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https://www.readbyqxmd.com/read/27913303/an-mtorc1-akt1-cathepsin-h-axis-controls-filaggrin-expression-and-processing-in-skin-a-novel-mechanism-for-skin-barrier-disruption-in-atopic-dermatitis
#1
Aishath S Naeem, Cristina Tommasi, Christian Cole, Stuart J Brown, Yanan Zhu, Benjamin Way, Saffron Ag Willis Owen, Miriam Moffatt, William O Cookson, John I Harper, Di Wl, Sara J Brown, Thomas Reinheckel, Ryan F L O'Shaughnessy
BACKGROUND: Filaggrin, encoded by the FLG gene, is an important component of the skin's barrier to the external environment and genetic defects in FLG strongly associate with Atopic Dermatitis (AD). However, not all AD patients have FLG mutations. OBJECTIVE: We hypothesised that these patients may possess other defects in filaggrin expression and processing, contributing to barrier disruption and AD, and therefore present novel therapeutic targets for this disease...
November 29, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27910524/spatially-resolved-thomson-scattering-measurements-of-the-transition-from-the-collective-to-the-non-collective-regime-in-a-laser-produced-plasma
#2
D B Schaeffer, C G Constantin, A S Bondarenko, E T Everson, C Niemann
We present optical Thomson scattering results that image for the first time in a single measurement the spatial transition from collective to non-collective scattering. Data were taken in the Phoenix laser laboratory at the University of California, Los Angeles. The Raptor laser was used to ablate a carbon plasma, which was diagnosed with the frequency-doubled Phoenix laser serving as a Thomson scattering probe. Scattered light was collected from the laser plasma up to 10 cm from the target surface and up to 10 us after ablation, and imaged with high spatial and spectral resolutions...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27909983/4-4-%C3%A3-resolution-cryo-em-structure-of-human-mtor-complex-1
#3
Huirong Yang, Jia Wang, Mengjie Liu, Xizi Chen, Min Huang, Dan Tan, Meng-Qiu Dong, Catherine C L Wong, Jiawei Wang, Yanhui Xu, Hong-Wei Wang
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics...
December 1, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27906700/update-on-lipid-species-and-paediatric-nonalcoholic-fatty-liver-disease
#4
Jake P Mann, Ariel E Feldstein, Valerio Nobili
PURPOSE OF REVIEW: To describe the recent advances in our understanding of fatty acids and lipids in paediatric nonalcoholic fatty liver disease (NAFLD) and their future implications. RECENT FINDINGS: Data have been accumulated to suggest that ceramides are the main drivers of hepatic insulin resistance in NAFLD, and inhibition of ceramide synthesis improves histology in mice.Saturated fatty acids formed by de novo lipogenesis generate increased lipotoxicity compared with dietary-derived saturated fatty acids...
November 30, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#5
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903908/ing1-regulates-rrna-levels-by-altering-nucleolar-chromatin-structure-and-mtor-localization
#6
Uma Karthika Rajarajacholan, Subhash Thalappilly, Karl Riabowol
Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of mTOR to modulate rRNA levels. ING1 represses rDNA transcription by recruiting HDAC1 to rDNA loci, increasing its association with the NoRC complex and deacetylating the histone H3K9 and H3K27 marks of active transcription. Loss of ING1 enhances nucleolar localization of phospho-mTOR and its association with Raptor and GβL, even during rapamycin treatment...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895121/neuronal-mtorc1-is-required-for-maintaining-the-nonreactive-state-of-astrocytes
#7
Yue Zhang, Song Xu, Kang-Yan Liang, Kai Li, Zhi-Peng Zou, Cui-Lan Yang, Kang Tan, Xiong Cao, Yu Jiang, Tian-Ming Gao, Xiao-Chun Bai
Astrocytes respond to central nervous system (CNS) insults through reactive astrogliosis, but the underlying mechanisms are unclear. In this study, we show that inactivation of mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller soma and fewer dendrites, resulting in microcephaly and aberrant behavior in adult mice...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27886809/small-mammal-utilization-by-middle-stone-age-humans-at-die-kelders-cave-1-and-pinnacle-point-site-5-6-western-cape-province-south-africa
#8
Aaron Armstrong
Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations...
December 2016: Journal of Human Evolution
https://www.readbyqxmd.com/read/27884298/mhy1485-activates-mtor-and-protects-osteoblasts-from-dexamethasone
#9
Sai Zhao, Caiyun Chen, Shouguo Wang, Feng Ji, Yue Xie
Dexamethasone (Dex) exerts cytotoxic effects to cultured osteoblasts. The potential effect of MHY1485, a small-molecular mammalian target of rapamycin (mTOR) activator, against the process was studied here. In both osteoblastic MC3T3-E1 cells and primary murine osteoblasts, treatment with MHY1485 significantly ameliorated Dex-induced cell death and apoptosis. mTOR inhibition, through mTOR kinase inhibitor OSI-027 or mTOR shRNAs, abolished MHY1485-mediated osteoblast cytoprotection against Dex. Intriguingly, activation of mTOR complex (mTORC1), but not mTORC2, is required for MHY1485's anti-Dex activity...
December 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27881705/essential-role-of-mtorc1-in-self-renewal-of-murine-alveolar-macrophages
#10
Wenhai Deng, Jialong Yang, Xingguang Lin, Jinwook Shin, Jimin Gao, Xiao-Ping Zhong
Alveolar macrophages (AMϕ) have the capacity of local self-renewal through adult life; however, mechanisms that regulate AMϕ self-renewal remain poorly understood. We found that myeloid-specific deletion of Raptor, an essential component of the mammalian/mechanistic target of rapamycin complex (mTORC)1, resulted in a marked decrease of this population of cells accompanying altered phenotypic features and impaired phagocytosis activity. We demonstrated further that Raptor/mTORC1 deficiency did not affect AMϕ development, but compromised its proliferative activity at cell cycle entry in the steady-state as well as in the context of repopulation in irradiation chimeras...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27879318/inactivation-of-raptor-mtorc1-signaling-in-osteoclasts-increases-bone-mass-by-inhibiting-osteoclast-differentiation-in-mice
#11
Qinggang Dai, Furong Xie, Yujiiao Han, Xuhui Ma, Siru Zhou, Lingyong Jiang, Weiguo Zou, Jun Wang
Mammalian target of rapamycin complex 1 (mTORC1) is involved in anabolic metabolism in both osteoblasts and chondrocytes, but the role of mTORC1 in osteoclast biology in vivo remains to be elucidated. In this study, we showed that deletion of regulatory-associated protein of mTOR (Raptor) in osteoclasts led to an increase in bone mass with decreased bone resorption. Raptor-deficient bone marrow-derived macrophages (BMMs) exhibited lower mTORC1-S6K1 signaling and retarded osteoclast differentiation as determined by the number of osteoclasts, TRAP activity and expression of osteoclast-specific genes...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27865265/monitoring-of-west-nile-virus-usutu-virus-and-meaban-virus-in-waterfowl-used-as-decoys-and-wild-raptors-in-southern-spain
#12
E Jurado-Tarifa, S Napp, S Lecollinet, A Arenas, C Beck, M Cerdà-Cuéllar, M Fernández-Morente, I García-Bocanegra
In the last decade, the number of emerging flaviviruses described worldwide has increased considerably, with wild birds acting as the main reservoir hosts of these viruses. We carried out an epidemiological survey to determine the seroprevalence of antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and Meaban virus (MBV), in waterfowl used as decoys and wild raptors in Andalusia (southern Spain), the region considered to have the highest risk of flaviviruses circulation in Spain...
December 2016: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/27863380/arctigenin-functions-as-a-selective-agonist-of-estrogen-receptor-%C3%AE-to-restrict-mtorc1-activation-and-consequent-th17-differentiation
#13
Xin Wu, Bei Tong, Yan Yang, Jinque Luo, Xusheng Yuan, Zhifeng Wei, Mengfan Yue, Yufeng Xia, Yue Dai
Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ERβ largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ERβ-dependent manner...
November 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27853552/using-areas-of-known-occupancy-to-identify-sources-of-variation-in-detection-probability-of-raptors-taking-time-lowers-replication-effort-for-surveys
#14
Campbell Murn, Graham J Holloway
Species occurring at low density can be difficult to detect and if not properly accounted for, imperfect detection will lead to inaccurate estimates of occupancy. Understanding sources of variation in detection probability and how they can be managed is a key part of monitoring. We used sightings data of a low-density and elusive raptor (white-headed vulture Trigonoceps occipitalis) in areas of known occupancy (breeding territories) in a likelihood-based modelling approach to calculate detection probability and the factors affecting it...
October 2016: Royal Society Open Science
https://www.readbyqxmd.com/read/27833856/avian-trichomonosis-in-spotted-owls-strix-occidentalis-indication-of-opportunistic-spillover-from-prey
#15
Krysta H Rogers, Yvette A Girard, Leslie Woods, Christine K Johnson
Avian trichomonosis, caused by the flagellated protozoan parasite Trichomonas gallinae, has variable pathogenicity among bird species ranging from asymptomatic infections to severe disease periodically manifesting in epidemic mortality. Traditionally, columbids are identified as highly susceptible to infection with occasional spillover into raptors that prey on infected birds. We identified avian trichomonosis in two dead California spotted owls (Strix occidentalis occidentalis) and three dead northern spotted owls (S...
December 2016: International Journal for Parasitology. Parasites and Wildlife
https://www.readbyqxmd.com/read/27821873/corrigendum-retinal-transcriptome-sequencing-sheds-light-on-the-adaptation-to-nocturnal-and-diurnal-lifestyles-in-raptors
#16
Yonghua Wu, Elizabeth A Hadly, Wenjia Teng, Yuyang Hao, Wei Liang, Yu Liu, Haitao Wang
No abstract text is available yet for this article.
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27817200/safe-application-of-regionalization-for-trade-in-poultry-and-poultry-products-during-highly-pathogenic-avian-influenza-outbreaks-in-usa
#17
David E Swayne, Rick E Hill, John Clifford
The 2014-15 H5Nx high pathogenicity avian influenza (HPAI) outbreak affected 211 commercial premises, 21 backyard flocks, 75 individual wild birds and four captive-reared raptors in 21 Western and upper Midwestern states, resulting in death or culling of over 50.4 million poultry in the stamping-out program that cost USA government $850 million. The outbreak had a negative $3.3 billion impact on the economy. Seventeen trading partners suspended imports of all U.S.-origin poultry and poultry products while 38 trading partners regionalized the United States, allowed trade in poultry and poultry products to continue from areas of the U...
November 7, 2016: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27807348/mtorc1-and-mtorc2-regulate-skin-morphogenesis-and-epidermal-barrier-formation
#18
Xiaolei Ding, Wilhelm Bloch, Sandra Iden, Markus A Rüegg, Michael N Hall, Maria Leptin, Linda Partridge, Sabine A Eming
Mammalian target of rapamycin (mTOR), a regulator of growth in many tissues, mediates its activity through two multiprotein complexes, mTORC1 or mTORC2. The role of mTOR signalling in skin morphogenesis and epidermal development is unknown. Here we identify mTOR as an essential regulator in skin morphogenesis by epidermis-specific deletion of Mtor in mice (mTOR(EKO)). mTOR(EKO) mutants are viable, but die shortly after birth due to deficits primarily during the early epidermal differentiation programme and lack of a protective barrier development...
October 27, 2016: Nature Communications
https://www.readbyqxmd.com/read/27796689/an-assessment-of-exposure-and-effects-of-persistent-organic-pollutants-in-an-urban-cooper-s-hawk-accipiter-cooperii-population
#19
Jason M Brogan, David J Green, France Maisonneuve, John E Elliott
Among the stressors confronting urban wildlife, chemical contaminants pose a particular problem for high trophic feeding species. Previous data from fortuitous carcass collections revealed surprisingly high levels of persistent organic pollutants in raptor species, including the Cooper's hawk (Accipiter cooperii), from urbanized areas of southwestern British Columbia, Canada. Thus, in 2012 and 2013, we followed up on that finding by measuring POPs in blood samples from 21 adult and 15 nestling Cooper's hawks in Vancouver, a large urban area in southwestern Canada...
October 28, 2016: Ecotoxicology
https://www.readbyqxmd.com/read/27793977/acute-stimulation-of-glucose-influx-upon-mitoenergetic-dysfunction-requires-lkb1-ampk-sirt2-and-mtor-raptor
#20
Dania C Liemburg-Apers, Jori A L Wagenaars, Jan A M Smeitink, Peter H G M Willems, Werner J H Koopman
Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A stimulated Glut1-mediated glucose uptake without altering Glut1 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation...
December 1, 2016: Journal of Cell Science
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