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981.
Fibroblast growth factor 21 (FGF21) plays an important role in energy homoeostasis. The unaddressed question of FGF21's effect on the development and progression of diabetic cardiomyopathy (DCM) is investigated here with FGF21 knockout (FGF21KO) diabetic mice. Type 1 diabetes was induced in both FGF21KO and C57BL/6J wild‐type (WT) mice via streptozotocin. At 1, 2 and 4 months after diabetes onset, the plasma FGF21 levels were significantly decreased in WT diabetic mice compared to controls. There was no significant difference between FGF21KO and WT diabetic mice in blood glucose and triglyceride levels. FGF21KO diabetic mice showed earlier and more severe cardiac dysfunction, remodelling and oxidative stress, as well as greater increase in cardiac lipid accumulation than WT diabetic mice. Western blots showed that increased cardiac lipid accumulation was accompanied by further increases in the expression of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and its target protein CD36, along with decreases in the phosphorylation of AMP‐activated protein kinase and the expression of hexokinase II and peroxisome proliferator‐activated receptor gamma co‐activator 1α in the heart of FGF21KO diabetic mice compared to WT diabetic mice. Our results demonstrate that FGF21 deletion‐aggravated cardiac lipid accumulation is likely mediated by cardiac Nrf2‐driven CD36 up‐regulation, which may contribute to the increased cardiac oxidative stress and remodelling, and the eventual development of DCM. These findings suggest that FGF21 may be a therapeutic target for the treatment of DCM.  相似文献   
982.
Zhang C  Gao Y 《Journal of biomechanics》2012,45(11):2001-2006
Most of the myofibers in long muscles of vertebrates terminate within fascicles without reaching either end of the tendon, thus force generated in myofibers has to be transmitted laterally through the extracellular matrix (ECM) to adjacent fibers; which is defined as the lateral transmission of force in skeletal muscles. The goal of this study was to determine the mechanisms of lateral transmission of force between the myofiber and ECM. In this study, a 2D finite element model of single muscle fiber was developed to study the effects of mechanical properties of the endomysium and the tapered ends of myofiber on lateral transmission of force. Results showed that most of the force generated is transmitted near the end of the myofiber through shear to the endomysium, and the force transmitted to the end of the model increases with increased stiffness of ECM. This study also demonstrated that the tapered angle of the myofiber ends can reduce the stress concentration near the myofiber end while laterally transmitting force efficiently.  相似文献   
983.
In recent years, the dominant biotype of Bemisia tabaci (Gennadius) has shifted from biotype B to Q in many locations of China. Our field monitoring showed that B. tabaci biotype Q could be found on pepper Capsicum frutescens L. while biotype B could not be found on the plant. To study the role of the host plant in the displacement of biotype B by Q, the adult mortality, female fecundity, and adult emergence of both biotypes B and Q on different host combinations were studied using a model system involving pepper and eggplant. The results showed that pepper is not a preferred host for either biotype B or Q adults in comparison with eggplant. The negative impact of pepper to biotype B is, however, much greater than that to biotype Q. Because both the survival rates of the adult whitefly and the average number of emerged adults per female of biotype Q on pepper are higher than that of biotype B, biotype Q showed higher fitness in comparison with biotype B. Our results suggest that the existence and differential impact of a nonpreferred host might affect the population fitness and therefore could play a role in the displacement of biotype B in some regions.  相似文献   
984.
Immune cell-mediated tissue injury is a common feature of different inflammatory diseases, yet the pathogenetic mechanisms and cell types involved vary significantly. Hypereosinophilic syndrome (HES) represents a group of inflammatory diseases that is characterized by increased numbers of pathogenic eosinophilic granulocytes in the peripheral blood and diverse organs. On the basis of clinical and laboratory findings, various forms of HES have been defined, yet the molecular mechanism and potential signaling pathways that drive eosinophil expansion remain largely unknown. In this study, we show that mice deficient of the serine/threonine-specific protein kinase NF-κB-inducing kinase (NIK) develop a HES-like disease, reflected by progressive blood and tissue eosinophilia, tissue injury, and premature death at around 25-30 wk of age. Similar to the lymphocytic form of HES, CD4(+) T cells from NIK-deficient mice express increased levels of Th2-associated cytokines, and eosinophilia and survival of NIK-deficient mice could be prevented completely by genetic ablation of CD4(+) T cells. Experiments based on bone marrow chimeric mice, however, demonstrated that inflammation in NIK-deficient mice depended on radiation-resistant tissues, implicating that NIK-deficient immune cells mediate inflammation in a nonautonomous manner. Surprisingly, disease development was independent of NIK's known function as an IκB kinase α (IKKα) kinase, because mice carrying a mutation in the activation loop of IKKα, which is phosphorylated by NIK, did not develop inflammatory disease. Our data show that NIK activity in nonhematopoietic cells controls Th2 cell development and prevents eosinophil-driven inflammatory disease, most likely using a signaling pathway that operates independent of the known NIK substrate IKKα.  相似文献   
985.
We have recently shown that effective cytokine gene therapy of solid tumors in HLA-A2 transgenic (HHD) mice lacking murine MHC class I molecule expression results in the generation of HLA-A2-restricted CD8(+) T effector cells selectively recognizing tumor blood vessel-associated pericytes and/or vascular endothelial cells. Using an HHD model in which HLA-A2(neg) tumor (MC38 colon carcinoma or B16 melanoma) cells are not recognized by the CD8(+) T cell repertoire, we now show that vaccines on the basis of tumor-associated blood vessel Ags (TBVA) elicit protective Tc1-dependent immunity capable of mediating tumor regression or extending overall survival. Vaccine efficacy was not observed if (HLA-A2(neg)) wild-type C57BL/6 mice were instead used as recipient animals. In the HHD model, effective vaccination resulted in profound infiltration of tumor lesions by CD8(+) (but not CD4(+)) T cells, in a coordinate reduction of CD31(+) blood vessels in the tumor microenvironment, and in the "spreading" of CD8(+) T cell responses to alternate TBVA that were not intrinsic to the vaccine. Protective Tc1-mediated immunity was durable and directly recognized pericytes and/or vascular endothelial cells flow-sorted from tumor tissue but not from tumor-uninvolved normal kidneys harvested from these same animals. Strikingly, the depletion of CD8(+), but not CD4(+), T cells at late time points after effective therapy frequently resulted in the recurrence of disease at the site of the regressed primary lesion. This suggests that the vaccine-induced anti-TBVA T cell repertoire can mediate the clinically preferred outcomes of either effectively eradicating tumors or policing a state of (occult) tumor dormancy.  相似文献   
986.
Recent findings have demonstrated an indispensable role for GM-CSF in the pathogenesis of experimental autoimmune encephalomyelitis. However, the signaling pathways and cell populations that regulate GM-CSF production in vivo remain to be elucidated. Our work demonstrates that IL-1R is required for GM-CSF production after both TCR- and cytokine-induced stimulation of immune cells in vitro. Conventional αβ and γδ T cells were both identified to be potent producers of GM-CSF. Moreover, secretion of GM-CSF was dependent on IL-1R under both IL-12- and IL-23-induced stimulatory conditions. Deficiency in IL-1R conferred significant protection from experimental autoimmune encephalomyelitis, and this correlated with reduced production of GM-CSF and attenuated infiltration of inflammatory cells into the CNS. We also find that GM-CSF production in vivo is not restricted to a defined CD4(+) T cell lineage but is rather heterogeneously expressed in the effector CD4(+) T cell population. In addition, inflammasome-derived IL-1β upstream of IL-1R is a critical regulator of GM-CSF production by T cells during priming, and the adapter protein, MyD88, promotes GM-CSF production in both αβ and γδ T cells. These findings highlight the importance of inflammasome-derived IL-1β and the IL-1R/MyD88 signaling axis in the regulation of GM-CSF production.  相似文献   
987.
Salmonella enterica serovar Typhimurium is one of the most prevalent serovars of Salmonella that causes human gastroenteritis. Here, we report the draft genome sequence of the S. Typhimurium multidrug-resistant strain ST1660/06. Comparative genomic analysis unveiled three strain-specific genomic islands that potentially confer the multidrug resistance and virulence of the strain.  相似文献   
988.
989.
We report the binding kinetics of fish-infected grouper nervous necrosis viruses (NNV) and selected antimicrobial peptides (AMPs) by nanomechanical detection. AMPs, the vital member in an innate immunity, are promising candidates in the fight against pathogens due to their broad range of antimicrobial activity and low toxicity. Grouper NNV primarily cause mass mortality of many marine cultured fish species, and two selected AMPs in this study were found to inhibit viruses by agglutinating its virions to form aggregates. The binding activity of NNVs with functionalized AMPs onto a sensing microcantilever yielded induced surface stresses, indicating high binding strength of molecular interaction. The binding affinity and kinetic rate constants of molecular recognition events calculated for NNV-AMP(TH1-5) compared to NNV-AMP(cSALF) were found to be 2.1-fold and 4.43-fold, respectively, indicating TH1-5 effectively bind with NNV more than cSALF. Moreover, a microscopic X-ray photoelectron spectroscopy technique was employed for further validation of pre- and post-NNV binding onto peptides-functionalized sensing surface. An increase in the spectrum and intensity of the P 2p and N 1s elements for the post-NNV binding was clearly shown to ensure the existence of phosphate groups and nitrogen-containing ring structures of specific NNV-TH1-5 interaction. Therefore, the microcantilever biosensing technique provides a potential and useful screening of AMPs for affinity to NNVs.  相似文献   
990.
A series of analogues of deoxyandrographolide (1) transformed by Cunninghamella blakesleana AS 3.2004 were isolated and identified by spectral methods including 2D NMR. Among them, 3-oxo-17,19-dihydroxy-7,13-ent-labdadien-15,16-olide (9), 3-oxo-19-hydroxy-1,13-ent-labdadien-15,16-olide (16), 3-oxo-1β-hydroxy-14-deoxy-andrographolide (17) and 3-oxo-2β-hydroxy-14-deoxyandrographolide (18) are new compounds. And their structure-activity relationships (SAR) of inhibitory activity on LPS-induced NO production in RAW 264.7 macrophage cells were also discussed.  相似文献   
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