De novo digenic mutations of telomere-associated proteins and inflammasomes initiate many chronic human diseases: a hypothesis [Hypothesis]
Many age-related human diseases have inflammatory components of uncertain causes. It has been proposed that some may be initiated or sustained by doubly mutated immune cells that have both inappropriately activated inflammasomes and enhanced replicative potential. Genes of cells that express mutant TERT and NLRP3 proteins are presumed to be at increased risk for mutagenesis because they reside in subtelomeric regions of chromatin that are deficient in DNA repair mechanisms. Expanded clones of proinflammatory cells can occur throughout one’s lifetime and could represent an alternative explanation for some forms of pat...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Marchesi, V. T. Tags: Hypothesis Source Type: research
Application and utility of mass cytometry in vaccine development [Review]
Mass cytometry enables highly multiplexed profiling of cellular immune responses in limited-volume samples, advancing prospects of a new era of systems immunology. The capabilities of mass cytometry offer expanded potential for deciphering immune responses to infectious diseases and to vaccines. Several studies have used mass cytometry to profile protective immune responses, both postinfection and postvaccination, although no vaccine-development program has yet systematically employed the technology from the outset to inform both candidate design and clinical evaluation. In this article, we review published mass cytometry ...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Reeves, P. M., Sluder, A. E., Paul, S. R., Scholzen, A., Kashiwagi, S., Poznansky, M. C. Tags: Review Source Type: research
A Crack At CRISPR: A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution by Jennifer A. Doudna and Samuel H. Sternberg Houghton Mifflin Harcourt, Boston, 2017 [Book Review]
(Source: FASEB Journal)
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Haselkorn, R. Tags: Book Review Source Type: research
The Fortunate Intersection of Schizophrenia and the Pill [Editorial]
(Source: FASEB Journal)
Source: FASEB Journal - January 2, 2018 Category: Biology Tags: Editorial Source Type: research
Erratum [Errata]
(Source: FASEB Journal)
Source: FASEB Journal - November 30, 2017 Category: Biology Tags: Errata Source Type: research
Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy [Research]
Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major facto...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Cascella, R., Fani, G., Capitini, C., Rusmini, P., Poletti, A., Cecchi, C., Chiti, F. Tags: Research Source Type: research
Anti-inflammatory effects of hypoxia-preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL-37 [Research]
Recent research has widely investigated the anti-inflammatory effects of mesenchymal stem cells and their secretory products, termed the secretome, in the treatment of multiple sclerosis (MS). The present study examined the capacity of the conditioned medium (CM) from human periodontal ligament stem cells (hPLSCs) under hypoxia (H-hPDLSCs-CM) to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. To induce EAE, female C57BL/6 mice were immunized with myelin oligodendroglial glycoprotein peptide35–55. At the onset of symptoms, H-hPDLSCs-CM was infused via the tail vein of mice. Our results ...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Giacoppo, S., Thangavelu, S. R., Diomede, F., Bramanti, P., Conti, P., Trubiani, O., Mazzon, E. Tags: Research Source Type: research
Neutrophil extracellular traps are critical for pregnancy loss in sphingosine kinase-deficient mice on 129Sv/C57BL/6 background [Research]
In this study, we demonstrated that NETs play a key role in the pathogenesis of sphingosine kinase (Sphk)-mediated pregnancy loss. Perturbing the sphingolipid pathway by disrupting Sphk genes during pregnancy led to excessive NET formation exclusively at the fetomaternal interface and early fetal death. Neutrophils that formed NETs were characterized by histone hypercitrullination and peptidylarginine deiminase 4 (PAD4) overexpression. In addition, thrombus formation was enhanced in the decidua, but not in the plasma, of Sphk-deficient mice. Blocking NET formation with a PAD4 inhibitor protected Sphk-deficient mice from pr...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Mizugishi, K., Yamashita, K. Tags: Research Source Type: research
Activation of liver X receptor suppresses angiogenesis via induction of ApoD [Research]
We examined the effects of T0901317, a potent LXR agonist, on angiogenesis of human umbilical vein endothelial cells (HUVECs). Treatment with T0901317 inhibited the tube formation and migration of HUVECs and reduced the in vivo angiogenesis, as determined by chorioallantoic membrane assay. T0901317 stimulated gene and protein expression of LXR target gene apolipoprotein D (ApoD). Overexpression of ApoD suppressed the tube formation of HUVECs. ApoD interacted with scavenger receptor class B member 1 (SR-B1), while knockdown of SR-B1 blocked suppressive effects of T0901317 on HUVEC migration. T0901317 treatment or overexpres...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Lai, C.-J., Cheng, H.-C., Lin, C.-Y., Huang, S.-H., Chen, T.-H., Chung, C.-J., Chang, C.-H., Wang, H.-D., Chuu, C.-P. Tags: Research Source Type: research
Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes [Research]
Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups—lean, overweight/obese (OW/OB), and OW/OB with T2DM—in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that aver...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Isherwood, C. M., Van der Veen, D. R., Johnston, J. D., Skene, D. J. Tags: Research Source Type: research
IL-17A deficiency mitigates bleomycin-induced complement activation during lung fibrosis [Research]
Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injury via TGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis. Microarray analyses of mRNA isolated from primary normal human small airway epithelial cells indicated that IL-17A (100 ng/ml; 24...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Cipolla, E., Fisher, A. J., Gu, H., Mickler, E. A., Agarwal, M., Wilke, C. A., Kim, K. K., Moore, B. B., Vittal, R. Tags: Research Source Type: research
Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways [Research]
Our previous studies have found that Growth factor receptor-bound protein 2–associated binding protein 2 (Gab2)—a docking protein—governs the development of fatty liver disease. Here, we further demonstrate that Gab2 mediates hepatocarcinogenesis. Compared with a faint expression in para-carcinoma tissue, Gab2 was highly expressed in ~60–70% of human hepatocellular carcinoma (HCC) specimens. Deletion of Gab2 dramatically suppressed diethylnitrosamine-induced HCC in mice. The oncogenic effects of Gab2 in HepG2 cells were promoted by Gab2 overexpression but were rescued by Gab2 knockdown. Furthermore,...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Cheng, J., Zhong, Y., Chen, S., Sun, Y., Huang, L., Kang, Y., Chen, B., Chen, G., Wang, F., Tian, Y., Liu, W., Feng, G.-S., Lu, Z. Tags: Research Source Type: research
Photoacoustic imaging for in vivo quantification of placental oxygenation in mice [Research]
Accurate analysis of placental and fetal oxygenation is critical during pregnancy. Photoacoustic imaging (PAI) combines laser technology with ultrasound in real time. We tested the sensitivity and accuracy of PAI for analysis of placental and fetal oxygen saturation (sO2) in mice. The placental labyrinth (L) had a higher sO2 than the junctional zone plus decidua region (JZ+D) in C57Bl/6 mice. Changing maternal O2 from 100 to 20% in C57Bl/6 mice lowered sO2 in these regions. C57Bl/6 mice were treated with the NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) from gestational day (GD) 11 to GD18 to induce hypert...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Yamaleyeva, L. M., Sun, Y., Bledsoe, T., Hoke, A., Gurley, S. B., Brosnihan, K. B. Tags: Research Source Type: research
Sepsis reveals compartment-specific responses in intestinal proliferation and apoptosis in transgenic mice whose enterocytes re-enter the cell cycle [Research]
This study sought to determine how stress alters these compartmentalized processes. Wild-type mice made septic via cecal ligation and puncture had decreased crypt proliferation and increased crypt and villus apoptosis. Fabpi-TAg mice expressing large T-antigen solely in villi had ectopic enterocyte proliferation with increased villus apoptosis in unmanipulated animals. Septic fabpi-TAg mice had an unexpected increase in villus proliferation compared with unmanipulated littermates, whereas crypt proliferation was decreased. Cell cycle regulators cyclin D1 and cyclin D2 were decreased in jejunal tissue in septic transgenic m...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Lyons, J. D., Klingensmith, N. J., Otani, S., Mittal, R., Liang, Z., Ford, M. L., Coopersmith, C. M. Tags: Research Source Type: research
