Difference in radiocarbon ages of carbonized material from the inner and outer surfaces of pottery from a wetland archaeological site

AMS (Accelerator Mass Spectrometry) radiocarbon dates for eight potsherds from a single piece of pottery from a wetland archaeological site indicated that charred material from the inner pottery surfaces (5052 ± 12 BP; N = 5) is about 90 14C years older than that from the outer surfaces (4961 ± 22 BP; N = 7). We considered three possible causes of this difference: the old wood effect, reservoir effects, and diagenesis. We concluded that differences in the radiocarbon ages between materials from the inner and outer surfaces of the same pot were caused either by the freshwater reservoir effect or by diagenesis. Moreover, we found that the radiocarbon ages of carbonized material on outer surfaces (soot) of pottery from other wetland archaeological sites were the same as the ages of material on inner surfaces (charred food) of the same pot within error, suggesting absence of freshwater reservoir effect or diagenesis

Protein Kinase B (Akt) Promotes Pathological Angiogenesis in Murine Model of Oxygen-Induced Retinopathy

Akt, or protein kinase B, is an important signaling molecule that modulates many cellular processes such as cell growth, survival, and metabolism. However, the vivo roles and effectors of Akt in retinal angiogenesis are not explicitly clear. We therefore detected the expression of Akt using Western blotting or RT-PCR technologies in an animal model of oxygen-induced retinopathy, and investigated the effects of recombinant Akt on inhibiting vessels loss and Akt inhibitor on suppressing experimental retinal neovascularization in this model. We showed that in the hyperoxic phase of oxygen-induced retinopathy, the expression of Akt was greatly suppressed. In the hypoxic phase, the expression of Akt was increased dramatically. No significant differences were found in normoxic groups. Compared with control groups, administration of the recombinant Akt in the first phase of retinopathy markedly reduced capillary-free areas, while the administration of the Akt inhibitor in the second phase of retinopathy significantly decreased retinal neovascularization but capillary-free areas. These results indicate that Akt play a critical role in the pathological process (vessels loss and neovascularization) of mouse model of oxygen-induced retinopathy, which may provide a valubale therapeutic tool for ischemic-induced retinal diseases

Ectopic Expression of E2F1 Stimulates β-Cell Proliferation and Function

OBJECTIVE-Generating functional beta-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G(1)- to S-phase transition during the cycling of many cell types and is required for pancreatic beta-cell growth and function. However, the consequences of overexpression of E2F1 in beta-cells are unknown. RESEARCH DESIGN AND METHODS-The effects of E2F1 overexpression on beta-cell proliferation and function were analyzed in isolated rat beta-cells and in transgenic mice. RESULTS-Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat beta-cells 20-fold but also enhanced beta-cell death. Coinfection with adenovirus Ad Akt expressing a constitutively active form of Akt (protein kinase B) suppressed beta-cell death to control levels. At 48 h after infection, the total beta-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of beta-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase beta-cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes. CONCLUSIONS-Overexpression of E2F1, either in vitro or in vivo, can stimulate beta-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult beta-cells, making it a strategic target for therapeutic manipulation of beta-cell function. Diabetes 59:1435-1444, 201

Increased Expression of Integrin-Linked Kinase Improves Cardiac Function and Decreases Mortality in Dilated Cardiomyopathy Model of Rats

AIMS: Integrin-linked kinase (ILK) is a multifunctional kinase linking the extracellular matrix to intracellular signaling pathways, whose activation in the heart gives rise to a number of functional consequences. The aim of this study is to demonstrate the therapeutic and survival benefit of cardiac ILK overexpression in a rat model of dilated cardiomyopathy. METHODS AND RESULTS: The dilated cardiomyopathy model was generated in rats by intraperitoneal administration of six equal doses of doxorubicin over a 2 week period. Five weeks after the first injection, echocardiographic analysis demonstrated impaired cardiac function and, at that point, recombinant adenoviral vector harboring ILK cDNA or vehicle was injected into the myocardium, and the rats re-studied 4 weeks later. Compared with vehicle injection, ILK treatment ameliorated inflammatory cell infiltration and cardiomyocyte degeneration, as well as left ventricular dilation and dysfunction. ILK treatment was also associated with a reduction in apoptosis and an increase in proliferation of cardiomyocytes, as well as decreased oxidative stress and autophagic vacuole accumulation. Importantly, mortality was lower in rats following ILK treatment than in those following vehicle injection. In cultured neonatal rat cardiomyocytes, we also found that ILK overexpression protected against doxorubicin-induced apoptosis, giving rise to an increase in their proliferation. CONCLUSIONS: These data demonstrate for the first time that ILK gene therapy improves cardiac function and survival in a model of dilated cardiomyopathy, and this may be mediated through suppression of inflammation, prevention of ventricular remodeling, inhibition of cardiomyocyte apoptosis and autophagy, and stimulation of cardiomyocyte proliferation

Modulation of Wnt5a Expression by Periodontopathic Bacteria

Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies

CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8αα T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8αα T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8αα colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system