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Derek D Jones, Brian T Gaudette, Joel R Wilmore, Irene Chernova, Alexandra Bortnick, Brendan M Weiss, David Allman
Little is known about the role of mTOR signaling in plasma cell differentiation and function. Furthermore, for reasons not understood, mTOR inhibition reverses antibody-associated disease in a murine model of systemic lupus erythematosus. Here, we have demonstrated that induced B lineage-specific deletion of the gene encoding RAPTOR, an essential signaling adaptor for rapamycin-sensitive mTOR complex 1 (mTORC1), abrogated the generation of antibody-secreting plasma cells in mice. Acute treatment with rapamycin recapitulated the effects of RAPTOR deficiency, and both strategies led to the ablation of newly formed plasma cells in the spleen and bone marrow while also obliterating preexisting germinal centers...
October 17, 2016: Journal of Clinical Investigation
Xingguang Lin, Jialong Yang, Jinli Wang, Hongxiang Huang, Hong-Xia Wang, Pengcheng Chen, Shang Wang, Yun Pan, Yu-Rong Qiu, Gregory A Taylor, Bruce A Vallance, Jimin Gao, Xiao-Ping Zhong
T-cells play an important role in promoting mucosal immunity against pathogens, but the mechanistic basis for their homeostasis in the intestine is still poorly understood. We report here that T-cell-specific deletion of mTOR results in dramatically decreased CD4 and CD8 T-cell numbers in the lamina propria of both small and large intestines under both steady-state and inflammatory conditions. These defects result in defective host resistance against a murine enteropathogen, Citrobacter rodentium, leading to the death of the animals...
October 12, 2016: Scientific Reports
Tamás Sticz, Anna Molnár, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Gyula Végső, Tamás Micsik, László Kopper, Anna Sebestyén
AIMS: Tumour heterogeneity and altered activation of signalling pathways play important roles in therapy resistance. The PI3K/Akt/mTOR signalling network is a well-known regulator of several functions that contribute to tumour growth. mTOR exists in two functionally different multiprotein complexes. We aimed to determine mTOR activity-related proteins in clinically followed, conventionally treated colon carcinomas and to analyse the correlation between clinical data and mTORC1 and mTORC2 activity...
October 11, 2016: Journal of Clinical Pathology
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
Megan Murgatroyd, Les G Underhill, Willem Bouten, Arjun Amar
Information on movement ecology is key in understanding the drivers and limitations of life history traits and has a potential role in indicating environmental change. Currently we have a limited understanding of the parameters of movement of territory-bound raptors, which are sensitive to environmental change. In this study we used GPS tracking technology to obtain spatially (within 3 m) and temporally (c. 3 mins) high-resolution movement data on a small sample of Verreaux's eagle Aquila verreauxii during the pre-laying period (n = 4) with one additional example during the chick rearing period...
2016: PloS One
Cong Li, Xiao-Dan Guo, Min Lei, Jia-Yi Wu, Jia-Zhen Jin, Xiao-Fan Shi, Zhi-Yuan Zhu, Vatcharin Rukachaisirikul, Li-Hong Hu, Tie-Qiao Wen, Xu Shen
AIM: Considering the complicated pathogenesis of Alzheimer's disease (AD), multi-targets have become a focus in the discovery of drugs for treatment of this disease. In the current work, we established a multi-target strategy for discovering active reagents capable of suppressing both Aβ level and Tau hyperphosphorylation from natural products, and found that the ethanol extract of Thamnolia vermicularis (THA) was able to improve learning ability in APP/PS1 transgenic mice by inhibiting both Aβ levels and Tau hyperphosphorylation...
October 3, 2016: Acta Pharmacologica Sinica
Roberta Lecis, Fabio Secci, Lucio Mandas, Marco Muzzeddu, Marco Pittau, Alberti Alberti
Mycoplasma spp. have been detected in birds of prey, but their prevalence in free living raptors and their significance to birds' health need further investigation. Molecular techniques have been increasingly used to identify mycoplasmas in various avian species, due to the fastidious nature of these pathogens hampering traditional bacteriologic tests. This study reports the identification of 23 novel mycoplasma sequences during the monitoring of 62 birds of prey on admission to wildlife centers in Sardinia, Italy...
September 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Bernard Escudier, Vincent Molinie, Sergio Bracarda, Pablo Maroto, Cezary Szczylik, Paul Nathan, Sylvie Negrier, Claudia Weiss, Camillo Porta, Viktor Grünwald, Laurence Albiges
BACKGROUND: Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe;, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). METHODS: This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient...
September 24, 2016: European Journal of Cancer
Ling-Lin Chen, Mei-Ling Wu, Feng Zhu, Jie-Jing Kai, Jing-Yin Dong, Xi-Mei Wu, Ling-Hui Zeng
AIMS: Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities. METHODS: Mice with conditional knockout of raptor protein were generated by cross-bred Rptor(flox/flox) mice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively...
September 28, 2016: CNS Neuroscience & Therapeutics
Aurore Val, Paloma de la Peña, Lyn Wadley
Here, we present direct taphonomic evidence for the exploitation of birds by hunter-gatherers in the Middle Stone Age of South Africa as far as ∼77 ka. The bird assemblage from Sibudu Cave, KwaZulu-Natal, was analysed for bone surface modifications. Cut-marks associated with skinning, defleshing, and disarticulation, perforations on distal humeri produced during disarticulation of the forewing, peeling, and human tooth marks were observed on bird bones (i.e., mostly pigeons, doves, Galliformes, waders, and raptors) recovered from pre-Still Bay, Still Bay, Howiesons Poort, and post-Howiesons Poort techno-complexes...
October 2016: Journal of Human Evolution
Yonghua Wu, Elizabeth A Hadly, Wenjia Teng, Yuyang Hao, Wei Liang, Yu Liu, Haitao Wang
Owls (Strigiformes) represent a fascinating group of birds that are the ecological night-time counterparts to diurnal raptors (Accipitriformes). The nocturnality of owls, unusual within birds, has favored an exceptional visual system that is highly tuned for hunting at night, yet the molecular basis for this adaptation is lacking. Here, using a comparative evolutionary analysis of 120 vision genes obtained by retinal transcriptome sequencing, we found strong positive selection for low-light vision genes in owls, which contributes to their remarkable nocturnal vision...
2016: Scientific Reports
Sukriti Krishan, Des R Richardson, Sumit Sahni
Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor that monitors ATP levels. There is also evidence that AMPK has onco-suppressive properties. Iron plays a crucial role in cellular energy transducing pathways and tumor cell proliferation. Therefore, metals (e.g., iron) could play an important role in the regulation of AMPK-dependent pathways. Hence, this investigation examined the effect of the iron and copper chelator and potent anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on the AMPK-mediated pathway...
September 15, 2016: Biochimica et Biophysica Acta
E Jurado-Tarifa, A Torralbo, C Borge, M Cerdà-Cuéllar, T Ayats, A Carbonero, I García-Bocanegra
Infections caused by thermotolerant Campylobacter spp. and Salmonella spp. are the leading causes of human gastroenteritis worldwide. Wild birds can act as reservoirs of both pathogens. A survey was carried out to determine the prevalence, genetic diversity and antimicrobial resistance of thermotolerant Campylobacter and Salmonella in waterfowl used as decoys and wild raptors in Andalusia (Southern Spain). The overall prevalence detected for Campylobacter was 5.9% (18/306; CI95%: 3.25-8.52) in decoys and 2...
October 2016: Comparative Immunology, Microbiology and Infectious Diseases
Christian H Gabriel, Fridolin Gross, Martin Karl, Heike Stephanowitz, Anna Floriane Hennig, Melanie Weber, Stefanie Gryzik, Ivo Bachmann, Katharina Hecklau, Jürgen Wienands, Johannes Schuchhardt, Hanspeter Herzel, Andreas Radbruch, Eberhard Krause, Ria Baumgrass
Transcription factors of the nuclear factor of activated T cell (NFAT)-family are essential for antigen-specific T cell activation and differentiation. Their cooperative DNA binding with other transcription factors, such as AP1-proteins (FOS, JUN, JUNB), FOXP3, IRFs and EGR1, dictate the gene regulatory action of NFATs. To identify as yet unknown interaction partners of NFAT, we purified biotin tagged NFATc1/αA, NFATc1/βC and NFATc2/C protein-complexes and analyzed their components by SILAC-based mass spectrometry...
September 16, 2016: Journal of Biological Chemistry
Adriana D Hernandez-García, Daniel A Columbus, Rodrigo Manjarín, Hanh V Nguyen, Agus Suryawan, Renán A Orellana, Teresa A Davis
Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation (PD) signaling in neonatal muscle during endotoxemia, overnight-fasted neonatal pigs were infused for 8 h with LPS or saline while plasma amino acids, glucose, and insulin were maintained at fasting levels during pancreatic-substrate clamps...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Samy L Habib, Anamika Yadav, Dawit Kidane, Robert Weiss, Sitai Liang
Exposure of renal cells to high glucose (HG) during diabetes has been recently proposed to be involved in renal injury. In the present study, we investigated a potential mechanism by which AICAR treatment regulates the DNA repair enzyme, 8-oxoG-DNA glycosylase (OGG1) in renal proximal tubular mouse cells exposed to HG and in kidney of db/db mice. Cells treated with HG for 2 days show inhibition in OGG1 promoter activity as well as OGG1 and Nrf2 protein expression. In addition, activation of AMPK by AICAR resulted in an increase raptor phosphorylation at Ser(792) and leads to increase the promoter activity of OGG1 through upregulation of Nrf2...
September 9, 2016: Cell Cycle
Ming Jiang, Xuejie Fu, Huilin Yang, Fanxin Long, Jianquan Chen
mTORC1 signaling has been shown to promote limb skeletal growth through stimulation of protein synthesis in chondrocytes. However, potential roles of mTORC1 in prechondrogenic mesenchyme have not been explored. In this study, we first deleted Raptor, a unique and essential component of mTORC1, in prechondrogenic limb mesenchymal cells. Deletion of Raptor reduced the size of limb bud cells, resulting in overall diminution of the limb bud without affecting skeletal patterning. We then examined the potential role of mTORC1 in chondrogenic differentiation in vitro...
September 8, 2016: Journal of Cellular Biochemistry
Meixiang Yang, Shasha Chen, Juan Du, Junming He, Yuande Wang, Zehua Li, Guangao Liu, Wanwen Peng, Xiaokang Zeng, Dan Li, Panglian Xu, Wei Guo, Zai Chang, Song Wang, Zhigang Tian, Zhongjun Dong
Activation of metabolic signalling by IL-15 is required for natural killer (NK) cell development. Here we show that Tsc1, a repressor of mTOR, is dispensable for the terminal maturation, survival and function of NK cells but is critical to restrict exhaustive proliferation of immature NK cells and activation downstream of IL-15 during NK cell development. Tsc1 is expressed in immature NK cells and is upregulated by IL-15. Haematopoietic-specific deletion of Tsc1 causes a marked decrease in the number of NK cells and compromises rejection of 'missing-self' haematopoietic tumours and allogeneic bone marrow...
2016: Nature Communications
Isis Victoriano Llopis, Laura Tomassone, Elena Grego, Emmanuel Serrano, Andrea Mosca, Gabriella Vaschetti, Daniela Andrade, Luca Rossi
BACKGROUND: The total contact rates (TCRs) between mosquito vectors and their potential hosts have a serious impact on disease transmission dynamics. Culex pipiens (sensu stricto) (s.s.) is considered the main vector of the West Nile Virus (WNV) in Europe and birds are the reservoir hosts. The results of our previous study showed that WNV seroreactors are significantly more prevalent among raptors compared to a range of other wild avian groups. The current study aims to assess the role of bird type (raptor vs others) and bird size on mosquito feeding preferences in a free-choice experiment using bird-baited traps...
2016: Parasites & Vectors
Lidia López-Jiménez, Julio Blas, Alessandro Tanferna, Sonia Cabezas, Tracy Marchant, Fernando Hiraldo, Fabrizio Sergio
In long-lived animals, the challenges that threaten individual homeostasis, and the way they are dealt with, are expected to vary in an age-related manner, encompassing the progressive selection of superior phenotypes and the acquisition and improvement of key skills (e.g. foraging, breeding and fighting abilities). Since exposure to homeostatic challenges typically elevates circulating glucocorticoid (GC) levels in vertebrates (modulating the behavioural and physiological responses that mediate allostasis), we may expect concomitant age-related changes in these hormones...
August 27, 2016: Oecologia
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