The Effect of Predictability on Subjective Duration

Events can sometimes appear longer or shorter in duration than other events of equal length. For example, in a repeated presentation of auditory or visual stimuli, an unexpected object of equivalent duration appears to last longer. Illusions of duration distortion beg an important question of time representation: when durations dilate or contract, does time in general slow down or speed up during that moment? In other words, what entailments do duration distortions have with respect to other timing judgments? We here show that when a sound or visual flicker is presented in conjunction with an unexpected visual stimulus, neither the pitch of the sound nor the frequency of the flicker is affected by the apparent duration dilation. This demonstrates that subjective time in general is not slowed; instead, duration judgments can be manipulated with no concurrent impact on other temporal judgments. Like spatial vision, time perception appears to be underpinned by a collaboration of separate neural mechanisms that usually work in concert but are separable. We further show that the duration dilation of an unexpected stimulus is not enhanced by increasing its saliency, suggesting that the effect is more closely related to prediction violation than enhanced attention. Finally, duration distortions induced by violations of progressive number sequences implicate the involvement of high-level predictability, suggesting the involvement of areas higher than primary visual cortex. We suggest that duration distortions can be understood in terms of repetition suppression, in which neural responses to repeated stimuli are diminished

Involvement of SOX-9 and FGF-23 in RUNX-2 regulation in osteoarthritic chondrocytes

Chondrocytes' hypertrophy includes metabolic changes, matrix remodelling, proliferation and apoptosis, characteristics associated with the progression of osteoarthritis. We investigated a possible association among Runt-related transcription factor 2 (RUNX-2), SOX-9 and fibroblast growth factor (FGF)-23 mRNA expressions in articular chondrocytes in order to elucidate their contribution in the osteoarthritic hypertrophic cartilage. SOX-9, FGF-23, RUNX-2 and matrix metalloproteinase (MMP)-13 mRNA expressions were evaluated in osteoarthritic and normal chondrocytes by real-time PCR whereas MMP-13 protein expression by immunofluorescense. RUNX-2, FGF-23 and SOX-9 were down-regulated using small interfering RNA technology and transfection with liposomes. The effect of human recombinant FGF-23 (hrFGF-23) on SOX-9 and RUNX-2 expression was tested in normal chondrocytes. We found higher expression of RUNX-2 and FGF-23 and a decreased expression of SOX-9 mRNA in osteoarthritic chondrocytes compared to normal (P < 0.0001). RUNX-2 down-regulation resulted in reduced MMP-13 expression in osteoarthritic chondrocytes and inhibition of SOX-9 in increased RUNX-2 and MMP-13 mRNA expression in normal chondrocytes, whereas inhibition of FGF-23 resulted in reduced RUNX-2 mRNA expression in osteoarthritic chondrocytes (all P < 0.0001). Silencing of RUNX-2 or FGF-23 did not affect SOX-9 mRNA levels in osteoarthritic chondrocytes. Moreover simultaneous down-regulation of SOX-9 and up-regulation of FGF-23 mRNA expressions in normal chondrocytes resulted in additive up-regulation of RUNX-2 mRNA expression. Treatment of normal chondrocytes with hrFGF-23 resulted in increased RUNX-2 mRNA expression, whereas it had no effect on SOX-9 mRNA expression. We demonstrated convincing associations among RUNX-2, SOX-9 and FGF-23 in relation to MMP-13 expression in osteoarthritic chondrocytes, contributing to a better understanding of the abnormal gene expression and cartilage degeneration processes associated with osteoarthritis

Increased levels of oxidative DNA damage in pesticide sprayers in Thessaly Region (Greece). Implications of pesticide exposure

The widespread use of pesticides substances nowadays largely guarantees the protection of crops and people from undesired pests. However, exposure to pesticides was related to a variety of human health effects. The present study was conducted in the region of Thessaly which is characterized by intensive agricultural activities and wide use of pesticides. The study aimed at estimating the oxidative damage to DNA in different subpopulations in Thessaly region (Greece) and investigating its correlation with exposure to pesticides and other potential risk factors. In total, the study involved 80 pesticide sprayers, 85 rural residents and 121 individuals, inhabitants of the city of Larissa. Demographic characteristics, habits, medical history and exposure history of the participants to pesticides were recorded by personal interviews. Blood and urine samples were collected from all participants. For the measurement of exposure to organophosphorus insecticides, dialkylphosphate (DAP) metabolites were quantified in urine, by gas chromatography-mass spectrometry. Genomic DNA was extracted from peripheral blood samples and the oxidation by-product 8-hydroxydeoxyguanosine (8-OHdG) was determined by Enzyme Immuno-Assay. Urinary metabolite concentrations were not associated with 8-OHdG levels but it was found that pesticide sprayers had significantly higher levels of 8-OHdG (p = 0.007) in comparison to the control group. Last season's exposure to insecticides and fungicides, expressed as total area treated multiplied by the number of applications, showed a statistically significant association with the risk of having high 8-OHdG levels [RR: 2.19 (95%CI:1.09-438) and RR: 232 (95% CI:1.16-4.64) respectively]. Additionally, from the subgroups of pesticides examined, seasonal exposure to neonicotinoid insecticides [RR: 2.22 (95% CI:1.07-4.63)] and glufosinate ammonium [RR: 326 (95% CI:1.38-7.69)] was found to have the greater impact on 8-OHdG levels. This study produced findings that support the hypothesis that pesticide exposure is involved in the induction of oxidative damage to DNA and identified chemical groups of pesticides which should be given greater attention in future investigations. (C) 2014 Elsevier B.V. All rights reserved

Life Cycle Costing Implementation in Green Public Procurement: A Case Study from the Greek Public Sector

Green Public Procurement (GPP) is an essential strategy for achieving goals related to public environmental policy, including sustainable production and consumption, streamlined use of resources and mitigation of climate change. The European Union has adopted policies towards &ldquo;greening&rdquo; public procurement for member states in order to promote environmental sustainability. Life Cycle Costing (LCC) is a method that measures the financial impact of an investment over the life cycle of a product. The current EU Procurement Directives (2014) are designed to position LCC centrally to sustainable sourcing. Although the literature identifies the links between the environmental dimension through GPP and the economic dimension through the use of LCC, the interaction between them in the context of public procurement has not been adequately captured. The aim of this paper is to evaluate the results of the LCC tools implementation in the context of GPP in Greece and study the economic impact of green procurement in public organizations. The urgent need of reducing energy consumption in the public sector due to the continuing energy crisis and climate change is an additional incentive to evaluate this impact. LCC tools developed by the EU were used, fed with data from public procurement contracts carried out in the Greek public sector. The results show that the adoption of environmental criteria requires market research, planning and coordination to make it cost-effective, especially under the legislative mandate of GPP in Greece by 2022

The immunopathogenetic role of autoantibodies in canine autoimmune hepatitis: Lessons to learn from human autoimmune hepatitis

Autoimmune hepatitis (AIH) is not a disease entity restricted to man, but it can be found in other animals including canines. An increasing number of studies have focused on the immunopathogenesis of human autoimmune hepatitis (hAIH), but little is known of what triggers canine autoimmune hepatitis (cAIH). Several drugs, toxins, microbial and viral agents are able to induce autoantibodies and indeed immune-mediated chronic canine hepatitis with immunological and serological features similar of those seen in the human disease. We discuss the features of cAIH paying attention to the autoantibody profile of the disease in comparison to that seen in hAIH. We also discuss the immunomodulatory role of specific molecular signaling pathways such as those mediated by tumor growth factor and p38 mitogen-activated kinase in the induction of AIH, and the potential of these molecules to act as targets of specialized immunotherapeutic interventions. Review of the literature indicates that we have more to learn for the delineation of autoantibody profile and the antigen-specific immunoregulatory mechanisms involved in the pathogenesis of cAIH from the human disease, rather than the other way around. © 2012 Springer-Verlag Italia

CUZD1 and Anti-CUZD1 Antibodies as Markers of Cancer and Inflammatory Bowel Diseases

CUZD1, the CUB, and zona pellucida-like domains-containing protein 1, is a newly identified antigen of pancreatic autoantibodies (PAB) giving a reticulogranular pattern in patients with inflammatory bowel diseases, and in particular Crohn's disease. The exact mechanisms by which this pancreatic antigen becomes the target of IBD-specific pancreatic autoantibodies are unclear. At the same time, evolving data strongly support a role for CUZD1 in carcinogenesis. Human CUZD1 is mapped at chromosome 10q26.13 and the loss of this region is a frequent event in various malignant tumours. mRNA overexpression of CUZD1 has been noted in ovarian cancer and serum levels of CUZD1 are elevated in women with ovarian cancer and patients suffering from pancreatic cancer. CUZD1 appears to be one of the relatively few biomarkers that serve as both cancer biomarker and autoantigen of autoantibodies in an autoimmune disease unrelated to cancerous organs. This review discusses the role of CUZD1 in cancer and autoimmunity. We anticipate that a better understanding of the function of CUZD1 will help us to understand how it becomes the focus of an autoimmune attack specifically targeting the intestine and its enigmatic role in carcinogenesis

Flow Cytometric Detection of p38 MAPK Phosphorylation and Intracellular Cytokine Expression in Peripheral Blood Subpopulations from Patients with Autoimmune Rheumatic Diseases

Flow cytometric analysis of p38 mitogen-activated protein kinase (p38 MAPK) signaling cascade is optimally achieved by methanol permeabilization protocols. Such protocols suffer from the difficulties to accurately detect intracellular cytokines and surface epitopes of infrequent cell subpopulations, which are removed by methanol. To overcome these limitations, we have modified methanol-based phosphoflow protocols using several commercially available antibody clones suitable for surface antigens, intracellular cytokines, and p38 MAPK. These included markers of B cells (CD19, CD20, and CD22), T cells (CD3, CD4, and CD8), NK (CD56 and CD7), and dendritic cells (CD11c). We have also tested surface markers of costimulatory molecules, such as CD27. We have successfully determined simultaneous expression of IFN-gamma, as well as IL-10, and phosphorylated p38 in cell subsets. The optimized phosphoflow protocol has also been successfully applied in peripheral blood mononuclear cells or purified cell subpopulations from patients with various autoimmune diseases. In conclusion, our refined phosphoflow cytometric approach allows simultaneous detection of p38 MAPK activity and intracellular cytokine expression and could be used as an important tool to study signaling cascades in autoimmunity

A case of keratomycosis caused by Curvularia spicifera (previously Bipolaris spicifera) and review of the literature

&lt;p&gt;Fungal keratitis is considered to be an important cause of visual impairment. We present a case of a-post-injury keratitis in a 29-year old male. Upon admission he presented with decreased visual acuity and a corneal ulcer. From the corneal tissue culture, Curvularia spicifera (formerly Bipolaris spicifera) was isolated and the identification was confirmed by molecular methods. The patient was treated with antifungal agents unsuccessfully, and keratoplasty was performed. To our knowledge this is the first case of Bipolaris keratomycosis reported in Greece and is indicative of the importance of early diagnosis for a favorable outcome.&lt;/p&gt

p38 mitogen-activated protein kinase (p38 MAPK)-mediated autoimmunity: Lessons to learn from ANCA vasculitis and pemphigus vulgaris

Evidence is beginning to accumulate that p38 mitogen activated protein kinase (p38 MAPK) signaling pathway plays an important role in the regulation of cellular and humoral autoimmune responses. The exact mechanisms and the degree by which the p38 MAPK pathway participates in the immune-mediated induction of diseases have started to emerge. This review discusses the recent advances in the molecular dissection of the p38 MAPK pathway and the findings generated by reports investigating its role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and autoimmune hepatitis. Application of newly-developed protocols based on sensitive flow cytometric detection has proven to be a useful tool in the investigation of the phosphorylation of p38 MAPK within different peripheral blood mononuclear cell populations and may help us to better understand the enigmatic role of this signaling cascade in the induction of autoimmunity as well as its role in immunosuppressive-induced remission. Special attention is paid to reported data proposing a specific role for autoantibody-induced activation of p38 MAPK-mediated immunopathology in the pathogenesis of autoimmune blistering diseases and anti-neutrophilic antibody-mediated vasculitides. (C) 2012 Elsevier B.V. All rights reserved