Physiological role of reactive oxygen species as promoters of natural defenses [Reviews]
It has been 60 yr since the discovery of reactive oxygen species (ROS) in biology and the beginning of the scientific community’s attempt to understand the impact of the unpaired electron of ROS molecules in biological pathways, which was eventually noted to be toxic. Several studies have shown that the presence of ROS is essential in triggering or acting as a secondary factor for numerous pathologies, including metabolic and genetic diseases; however, it was demonstrated that chronic treatment with antioxidants failed to show efficacy and positive effects in the prevention of diseases or health complications that re...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Roy, J., Galano, J.-M., Durand, T., Le Guennec, J.-Y., Lee, J. C.-Y. Tags: Reviews Source Type: research

Nutritional interventions and the IL-6 response to exercise [Reviews]
IL-6 is a pleiotropic cytokine with a wide range of biologic effects. In response to prolonged exercise, IL-6 is synthesized by contracting skeletal muscle and released into circulation. Circulating IL-6 is thought to maintain energy status during exercise by acting as an energy sensor for contracting muscle and stimulating glucose production. If tissue damage occurs, immune cells infiltrate and secrete cytokines, including IL-6, to repair skeletal muscle damage. With adequate rest and nutrition, the IL-6 response to exercise is attenuated as skeletal muscle adapts to training. However, sustained elevations in IL-6 due to ...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Hennigar, S. R., McClung, J. P., Pasiakos, S. M. Tags: Reviews Source Type: research

Fifty years in human genetics--a career retrospective [Perspective]
(Source: FASEB Journal)
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Kazazian, H. H. Tags: Perspective Source Type: research

The Hemoglobinopathies: An Empowering Era of Human Genetics in the Clinic and the Laboratory [Editorial]
(Source: FASEB Journal)
Source: FASEB Journal - August 31, 2017 Category: Biology Tags: Editorial Source Type: research

Erratum [Erratum]
(Source: FASEB Journal)
Source: FASEB Journal - August 1, 2017 Category: Biology Tags: Erratum Source Type: research

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model [Research]
Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelia...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Tags: Research Source Type: research

Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease [Research]
Plasma endothelial cell–derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycoprotein VI. EDE levels of VCAM-1, von Willebrand factor, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, and lysyl ox...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Goetzl, E. J., Schwartz, J. B., Mustapic, M., Lobach, I. V., Daneman, R., Abner, E. L., Jicha, G. A. Tags: Research Source Type: research

Filamin A is required for spindle migration and asymmetric division in mouse oocytes [Research]
In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels. Moreover, FLNA knockdown reduced the phosphorylation of cofilin and Rho kinase (ROCK) near the spindle. Similar phenotypes, such as decreased filament actin levels, impaired spindle migration and polar body extrusion, were ...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Wang, H., Guo, J., Lin, Z., Namgoong, S., Oh, J. S., Kim, N.-H. Tags: Research Source Type: research

Potentiation of receptor responses induced by prolonged binding of G{alpha}13 and leukemia-associated RhoGEF [Research]
In this study, we focused on the signaling from GPCRs to RhoA via Gα13 and leukemia-associated RhoGEF (LARG). The activation of Gα13 was elucidated in living cells with high temporal and spatial resolution by means of FRET. The inactivation after agonist withdrawal occurred in the same range (t1/2 = 25.3 ± 2.2 s; mean ± sem; n = 22) as described for other Gα proteins. The interaction of Gα13 and LARG and the thereby-induced LARG translocation to the plasma membrane were at least 1 order of magnitude more stable after agonist withdrawal, exceeding Gα13 deactivation in the absence ...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Bodmann, E.-L., Krett, A.-L., Bünemann, M. Tags: Research Source Type: research

Strenuous exercise triggers a life-threatening response in mice susceptible to malignant hyperthermia [Research]
In humans, hyperthermic episodes can be triggered by halogenated anesthetics [malignant hyperthermia (MH) susceptibility] and by high temperature [environmental heat stroke (HS)]. Correlation between MH susceptibility and HS is supported by extensive work in mouse models that carry a mutation in ryanodine receptor type-1 (RYR1Y522S/WT) and calsequestrin-1 knockout (CASQ1-null), 2 proteins that control Ca2+ release in skeletal muscle. As overheating episodes in humans have also been described during exertion, here we subjected RYR1Y522S/WT and CASQ1-null mice to an exertional-stress protocol (incremental running on a treadm...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Michelucci, A., Paolini, C., Boncompagni, S., Canato, M., Reggiani, C., Protasi, F. Tags: Research Source Type: research

13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis [Research]
Rheumatoid arthritis is an inflammatory condition characterized by overzealous inflammation that leads to joint damage and is associated with an increased incidence of cardiovascular disease. Statins are frontline therapeutics for patients with cardiovascular disease and exert beneficial actions in rheumatoid arthritis. The mechanism that mediates the beneficial actions of statins in rheumatoid arthritis remains of interest. In the present study, we found that the administration of 2 clinically relevant statins—atorvastatin (0.2 mg/kg) or pravastatin (0.2 mg/kg)—to mice during inflammatory arthritis up-regulate...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Walker, M. E., Souza, P. R., Colas, R. A., Dalli, J. Tags: Research Source Type: research

Folate-dependent methylation of septins governs ciliogenesis during neural tube closure [Research]
We report that methylation of septin2 affected its GTP binding activity and formation of the septin2-6-7 complex. We propose that folic acid promotes normal NTC in some embryos by regulating the methylation of septin2, which is critical for normal cilium formation during early embryonic development.—Toriyama, M., Toriyama, M., Wallingford, J. B., Finnell, R. H. Folate-dependent methylation of septins governs ciliogenesis during neural tube closure. (Source: FASEB Journal)
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Toriyama, M., Toriyama, M., Wallingford, J. B., Finnell, R. H. Tags: Research Source Type: research

Peroxisome proliferator-activated receptor-{gamma} agonists attenuate biofilm formation by Pseudomonas aeruginosa [Research]
Pseudomonas aeruginosa is a significant contributor to recalcitrant multidrug-resistant infections, especially in immunocompromised and hospitalized patients. The pathogenic profile of P. aeruginosa is related to its ability to secrete a variety of virulence factors and to promote biofilm formation. Quorum sensing (QS) is a mechanism wherein P. aeruginosa secretes small diffusible molecules, specifically acyl homo serine lactones, such as N-(3-oxo-dodecanoyl)-l-homoserine lactone (3O-C12-HSL), that promote biofilm formation and virulence via interbacterial communication. Strategies that strengthen the host’s abi...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Bedi, B., Maurice, N. M., Ciavatta, V. T., Lynn, K. S., Yuan, Z., Molina, S. A., Joo, M., Tyor, W. R., Goldberg, J. B., Koval, M., Hart, C. M., Sadikot, R. T. Tags: Research Source Type: research

Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane-derived noncollagenous 1 domain peptide [Research]
We report our findings that NC1 domain derived from collagen α3(IV) chain—a major structural component of the BM—was capable of inducing BTB remodeling, making the BTB leaky in studies in vivo. Furthermore, NC1 domain peptide was transported across the epithelium via a microtubule-dependent mechanism and is capable of inducing apical ES degeneration, which leads to germ cell exfoliation from the seminiferous epithelium. Of more importance, we show that NC1 domain peptide exerted its regulatory effect by disorganizing actin microfilaments and microtubules in Sertoli cells so that they failed to support cel...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Chen, H., Mruk, D. D., Lee, W. M., Cheng, C. Y. Tags: Research Source Type: research

Modeled structural basis for the recognition of {alpha}2-3-sialyllactose by soluble Klotho [Research]
Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that contains 2 extracellular domains KL1 and KL2, each of which shares sequence homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses with a poorly understood mechanism of action. Notably, in injury settings, sKlotho confers cardiac and renal protection by down-regulating calcium-permeable transient receptor potential canonical type isoform 6 (TRPC6) channels in cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed th...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Wright, J. D., An, S.-W., Xie, J., Yoon, J., Nischan, N., Kohler, J. J., Oliver, N., Lim, C., Huang, C.-L. Tags: Research Source Type: research