The recognition and lyses of tumor cells by NK cells are extremely important in innate immunity against tumors. Since their discovery, a large number of studies have demonstrated that NK cell-mediated lyses of different types of tumor cells in vitro, as well as NK cell- dependent elimination of many tumors in vivo (Ljunggren, 2008). NK cells are capable of inducing lyses of cells showing decreased expression of Major Histocompatibility Complex (MHC) class I on their surface (e.g.: Tumor cells). The decrease of MHC I molecules on the cell surface prevents it to be recognized and lysed by specific Cluster of Differentiation (CD8+) T lymphocytes. In this context, the function of NK cells becomes necessary in combating carcinogenesis (Garay et al., 2007; Maccalli et al., 2009). Once activated, NK cells release several cytokines, especially IFN-γ. Moreover, NK cells release perforin inducing pores formation in tumor cells during the process of cytotoxicity, similarly to that played by CD8+ T lymphocytes (Abbas et al., 2011; Maccalli et al., 2009). NK cells also produce TNF-α, TNF-β and GM-CSF (granulocyte macrophage-colony factor) stimulant (Vivier et al., 2011). NK cells express CD56 and CD16. Dalmazzo et al. (2009) associated the expression of CD56/CD16 with worse prognosis for T-cell acute lymphoblastic leukaemia.
In spite of all advances supporting the cross-relationships between iron and adaptive immunity, many questions still remain unexplored and may keep immunologists and iron biologists busy for some time. Among them, perhaps the most critical question relates to the HFE function and how does it impact simultaneously on iron metabolism and on the adaptive immune functions. Interestingly, 20 years before the discovery of HFE, Svejgaard and Ryder postulated that HLA alloantigens could interfere with ligand/receptor interactions not directly involved in immune reactions, and those interactions could under certain conditions explain some associations between HLA and non- immunological diseases giving as an example hemochromatosis . This view came to be vindicated with the demonstration that HFE, a non-classical HLA molecule, interacts with both the TfR1 to regulate transferrin-mediated iron uptake  and with transferrin receptor 2 (TfR2) as an iron sensor for hepcidin signaling . The role of HFE, however, is not limited to iron metabolism; it is also implicated in adaptive immune functions. Sometime ago, it was suggested that HFE could be immunogenic , and more recently Reuben and co-workers proposed that HFE could have a role in antigen processing and presentation leading to an inhibition of CD8+ T-lymphocyte activation . These were in vitro studies based on several T-lymphocyte activation read-outs in cells transfected with wild type and mutated HFE molecules. The first demonstration in vivo that HFE acts as a negative regulator of CD8+ T-lymphocyte activation and differentiation was provided with the study by Costa et al.  of lymphocyte gene expression signatures from HFE-related hemochromatosis patients and mouse models, where it was shown that the lack of HFE impacts on several activation markers in CD8+ T lymphocytes . Whatever the mechanism how this interaction may happen, it may imply the cross-talk between HFE and the MHC class I antigen presentation pathway, as suggested by Almeida et al in their study of peripheral blood mononuclear cells from patients
Total RNA of heart was extracted from WT mice and Olr1 KO mice. Microarray analysis was performed by Affymetrix Mouse Genome GenChip 430 2.0 gene expression array (Affymetrix Inc. Santa Clara, CA) and analyzed using Affymetrix Microarray Analysis Suite (MAS) 5.0 to assess the quality of RNA and hybridization. A log base 2 transformation was applied to the data before the arrays were normalized. All values from each array were normalized to the 75th percentile value of the array, which was arbitrarily set at intensity minimum .100. For gene ex- pression annotation, EASE (as described in http://apps1.niaid. nih.gov/David) analysis was performed on significant genes identified by one sample t-test. In addition, Gene Ontology (GO) terms http://www.geneontology.org) for biological processesand cellular component were identified as proposed by the GO Consortium. All microarray data is MIAME compliant and that the raw data has been deposited in a MIAME compliant database (ArrayExpress) as detailed on the MGED Society website http:// www.mged.org/Workgroups/MIAME/miame.html (accession number E-MTAB-473).
Epigenetic modifications are a common feature of PCa and play an important role in prostate carcinogenesis as well as in disease progression. Even though aberrant DNA methylation is the best-studied cancer-related epigenetic alteration in PCa, the study of alterations in chromatin remodeling and miRNA regulation constitute a growing research field that will provide an overall view of the PCa epigenome as well as of the interaction between epigenetic and genetic mechanism involved in prostate carcinogenesis. Two important recent discoveries were made: The presence of resident microbial species in the urinary tract and their role in the initiation of chronic inflammation, PIA and development of PCa. Facts that may explain the higher prevalence of PCa in the western countries include elevated inflammation due to metabolic syndrome and associated comorbidities. It is essential to completely characterize the linkbetween these facts - chronic prostatic inflammationand epigenetic alterations - to allow the development of strategies for PCa prevention.
Oxidative stress is thought to play an important role in the development of MS . Although the level of MDA was not significantly different between the case and control groups, the activities of CAT, SOD, and GPx were significantly lower in the case group (Figure 2). In the present study, we also assessed the correlations between inflammatory markers and oxidative stress makers. We observed that the inflammatory markers were significantly correlated with increased oxidative stress (Table 3). In particular, subjects with higher inflammation status (hs-CRP $3.0 mg/L) had significantly higher MDA level and lower antioxidant enzymes activities (data not shown). There was a significant positive correlation betweeninflammation status and oxidative stress, and we presume that subjects with MS may have a higher inflammation status and a higher level of oxidative stress. Antioxidant enzymes are the first line of defense against ROS and lead to a decrease in their activities . In addition, MS subjects in general were typically abdominally obese. In the present study, Table 4. The odds ratios of metabolic syndrome based on
Adipose tissue produces a range of adipokines that are directly involved in insulin resistance . Herein, we showed that MK suppressed insulin signaling in adipocytes, as indicated by reduced phosphorylation of Akt and IRS-1 in response to insulin stimulation. These findings provide the first evidence that MK may be a novel inducer of insulin resistance. Since MK expression was increased in adipose tissue of obese mice, it warrants further investigation whether MK induces insulin resistance in vivo. Moreover, as serum MK levels were significantly elevated in obese subjects and correlated with BMI, further analysis of its relationship with insulin sensitivity will provide additional evidence for its actions on insulin resistance in humans. In addition, given the chemotactic activities of MK towards macrophages , which play a central role in obesity-induced inflammationand insulin resistance , future studies will also investigate the involvement of MK in macrophage recruitment into adipose tissue during obesity.
We have presented the various stages of our concept of how CMEs are linked to the evolution of filament channel and fil- ament magnetic fields and have summarized these stages in Fig. 3. We assume that the parts of this concept will be tested in future observational and theoretical research. Principal among the many questions that need to be addressed are: (1) Is there a quantitative relationship between the amount of canceling magnetic flux observed in a specific filament channel during the lifetime of a filament, the energy in this magnetic flux, and the energy needed to cause the overlying corona to expand at the observed rate? (2) Can photospheric magnetic reconnection be simulated quantitatively and real- istically? (3) In high resolution observations, can the initial input of mass into filaments and the draining of mass out of filaments be observed? (4) Can the input of small knots of mass into filament threads be associated with the rate and regularity of canceling magnetic fields?
Serum samples from 87 calves from a dairy herd in Southern Brazil were collected to determine the levels of passive transfer and its relationship to morbidity and mean daily weight gain (MDG). Serum immunoglobulin (Ig) levels were measured by the zinc sulfate turbidity test at 24 hours of age in the calves. The average serum Ig level was 11.40g/". Fourteen out of 87 calves (16.1%) showed serum Ig levels one standard deviation below the mean (4.59g/") and were considered as having failure of passive immunity transfer (FPT). The occurrence of diarrhea from birth to weaning was higher in the FPT group (100%) than the normal group (90.7%) but the difference was not significant. The occurrence of signs of respiratory disease was similar in both groups (35.7% for FPT and 36.9% for the normal group). The mean daily gain from birth to 13-16 months of age in the FPT group was significantly (P>0.05) lower than in the group with normal serum Ig levels. The difference in MDG from birth to weaning between the groups was not significant. These results demonstrate the importance of passive immunityin cattle, and also provide regional parameters for the evaluation of FPT in cattle.
The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased eficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep- deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modiied release of adipokines result- ing from sleep deprivation could lead to a chronic sub-inlammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.
A female, 53-year-old patient was sub- mitted, on an outpatient basis, to a proce- dure of intramammary injection of hyalu- ronic acid-based gel (Macrolane) for breast augmentation for 18 months ago. During the procedure a single point on the skin of each breast was utilized for insertion of the needle. The patient was referred to the au- thors’ institution for investigation of bilat- eral, painless, palpable nodules whose on- set occurred after the procedure. Breast ultrasonography demonstrated the presence of multiple, predominantly anechoic, ovoid, cyst-like collections containing low- amplitude echoes, in intramuscular and intraglandular locations (Figure 1), with no INTRODUCTION
Tumors often arise in sites of chronic inflammation , which provide a microenvironment containing various mediators (e.g., cytokines, chemokines, and prostaglandins) with tumor- promoting properties, including enhanced cell proliferation, survival, angiogenesis and migration. In this context, Haybaeck and co-workers have found the involvement of LTβR signaling in the development of virus-induced chronic hepatitis and hepatocellular carcinoma (HCC) . In hepatic primary tissue from hepatitis B or C (HBV- or HCV)-induced chronic hepatitis and HCC patients, these authors found upregulation of not only LTβR and its ligands (LTα, LTβ and LIGHT) but also pro-inflammatory chemokines (CCL2, CCL3 and CXCL10). LTBR was highly expressed in liver cell populations depleted of hematopoietic (CD45-positive) cells, while LTA, LTB and LIGHT were expressed both in hematopoietic and non-hematopoietic HCV-induced hepatitis and HCC liver cell fractions. Furthermore, expression of LTBR, LTA, LTB, LIGHT and inflammatory chemokines in a human hepatocyte cell line Huh-7.5 was shown to be directly linked to the presence of HCV infection. In transgenic mice expressing high levels of LTα and LTβ in a liver-specific manner, LTβR signaling induced chronic hepatitis characterized by inflammation, T and B lymphocytic infiltrates and hepatocyte apoptosis. Further experiments demonstrated that T and B cells, which express LTβR ligands, and LTβR-mediated canonical NF-κB signaling activation in hepatocytes were both required for LTβR-induced chronic hepatitis and HCC development . These findings indicate that persistent lymphocyte-derived LTα 1 β 2 and
For a better understanding of International Large-Scale Assess- ment, we use as reference the distinction proposed by Nóvoa and Yariv- Mashal (2003): in the first case the assessment programmes focusing on comparison of national cases without a specific time space context; in the second case the comparison focusing on studies of variables, that confront results of different sets of variables. According to Lindblad, Pettersson and Popkewitz (2015), the first perspective is linked to hu- man sciences (particularly this heuristic is used by the disciplines of literature or science of educational field); the second one is related to social sciences (this second paradigm is more developed in sociology of education, economy of educational or social statistics field). This kind of debate developed, also in comparative studies field (Steiner-Khamsi, 2013). Lindblad, Pettersson and Popkewitz (2015) propose several ex- amples. Standardised comparisons measure outcomes against norms, school indicators and gender equality. Amongst those type programmes there are, for examples International Large-Scale Assessment (ILSA). The International Large-Scale Assessment, which is an assessment based on standardised tools that promote the comparison of pupils’ or adult’s knowledge and competencies in different countries in the world. The agencies that designed and further implement this kind of assessments are Association for the Evaluation of Educational Achievement (IEA) and the OCDE.
The factors driving GS variation remain a largely controversial issue. Several competing models have been proposed to explain among-species variations in GS. Interestingly, at least two of these models involve population genetic processes that may drive GS variation within species among populations, and ultimately preside over among-species GS variation (Agren & Wright, 2011; Petrov, 2001). The ‘‘mutational hazard’’ hypothesis (Lynch et al., 2011) posits that selection to maintain a constant per-genome mutation rate indirectly impacts GS. Providing that selection overcomes drift, the per base-pair-per-generation mutation rate correlates negatively with GS (Sung et al., 2012). Under this model, one expects within-species GS variation to be driven by differences in effective population size that condition the efficiency of natural selection against genome expansion. An alternative hypothesis asserts that positive natural selection may indirectly influence GS variation through developmental or adaptive phenotypes (Knight & Beaulieu, 2008). In plants, the latter hypothesis has been sustained by a handful of empirical studies demonstrating that GS correlates negatively with development traits such as seedling (Mowforth & Grime, 1989), root meristem growth rate (Gruner et al., 2010), and cell cycle length (Francis, Davies & Barlow, 2008). Small genomes indeed presumably facilitate faster cell division and therefore a higher growth rate (Knight, Molinari & Petrov, 2005; Rayburn, Dudley & Biradar, 1994).
cultures were then centrifuged at 3 500 g for 5 min at room temperature, resuspended in 30 ml of Resuspension Medium (T0) and grown at 37ºC and 180 rpm for the remaining assay’s length. In the case of strain containing gfp fusions, 1 ml samples were collected at the indicated times and centrifuged for 2 min at 3 500 g. The sediment was resuspended in 100 μl of PBS buffer 1X and FM4-64 (membrane dye from Molecular Probes) was added to a concentration of 10 μg/ml. In the case of strain containing SNAP-tag fusions 0.2 ml samples were taken and incubated with SNAP-tag substrate added at a final concentration of 250 nM (505-STAR, New England biolabs). Samples were incubated in the dark for 30 min at 37ºC and then centrifuged for 2 min at 3 500 g. The sediment was resuspended in 1 ml of PBS buffer 1X and FM4-64 was added to a concentration of 10 μg/ml. The solutions were then centrifuged for 2 min at 3 500 g and resuspended in 10 µl. 3 µl of each sample were then applied in a agarose (1.7%) slide and observed in bright phase contrast and fluorescence at 1600X with a Leica SM6000B microscope. Images were taken with a cooled camera iXon-em+885 (Andor Technology) and analysed with Methamorph (Molecular devices) and Adobe Photoshop CS6 version 13.0 (Adobe Systems Incorporated). Standard filters for GFP (green) and FM4-64 (red) were used for collecting the fluorescence images. For quantification of the gfp signal resulting from transcriptional fusions, 6x6 pixel regions were defined in the desired cell and the average pixel intensity was calculated, and corrected by subtracting the average pixel intensity of the background.
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Thecases in which they frequentlyusedecentralizationare: *The desire toincrease the participation ofthe populationandbecause of itsgreat importancein achieving thedecisions and policiesbe realisticandsome of the propertiesthat helpin the success ofdevelopment policiesto reachtheir goals Messahaalarge size ofpopulationandthe stateso that it cannotaddressthe centralpolicies ofeachsprawlingspaceissueswhich forces theupperbodies of theplanningmake room fordecentralizedmanagement styleandtakethe brunt ofthe most important inthe process of preparingdevelopment plans Multiplicity ofnationalities andracesas it isin such circumstancesbeuniting of interestsis not possible orfar-fetchedprocess, which requires giving
QYHJ, a seven-herb Chinese medicinal formula, comprised Scutellria barbata (Ban zhi lian), Heydyotis diffusa (Bai hua she she cao), Amorphophallus kiusianus (She liu gu), Coix lacryma-jobi (Yi ren), Gynostemma pentaphyllum (Jiao gu lan), Ganoderma luncidum (Ling zhi) and Amomum cardamomum (Bai dou kou). QYHJ was prepared as previouly decribed [14–16]. Briefly, powders of QYHJ formula were produced by Jiang-yin Tianjiang Pharmaceutical Co, Ltd. To ensure standardization and maintain interbatch reliability of QYHJ, a high performance liquid chromatography (HPLC) chromatographic fingerprint was developed for its quality control. The fingerprint chromatograms of QYHJ formula was shown in Figure S1. The final decoction of QYHJ was prepared by dissolving the herbal powder in distilled water to the required concentration. The daily dosage for nude mice was 18 g/kg, as calculated according to the following human-mouse transfer formula Db = Da6(Rb/Ra)6(Wb/Wa)2/3, where D, R, and W represent dosage, shape coefficient, and body weight, respectively, and a and b represent human and mouse, respectively. Human recombinant interleukin-6 (IL-6) was obtained from R&D Systems (R&D Systems) and dissolved in sterile PBS containing 2% bovine serum albumin (BSA). The following antibodies were used: rabbit anti-E-cadherin, anti-vimentin, anti-N-cadherin and anti-Slug (Cell Signaling Technology, Beverly, MA); rabbit anti-CD68 (Santa Cruz Biotechnology, Santa Cruz, CA); goat anti-IL-6 (Santa Cruz Biotechnology, Santa Cruz, CA, USA); GAPDH (Epitomics, Burlingame, CA).
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease of unknown etiology that affects multiple organs and is associated with the production of several different autoantibodies. It is a systemic inflammatory disease susceptibility to which is associated with genetic and environmental factors . Genetic risk factors for SLE include alleles in IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and others [2,3,4]; the functional role of the polymorphisms as well as the relationships with other autoimmune diseases such as rheumatoid arthritis were suggested[5,6]. Espe- cially, altered frequencies of human leukocyte antigen (HLA) alleles are known to be associated with SLE. Some HLA-DRB1 alleles are reported to be positively associated with SLE susceptibility in several ethnic groups studied: DRB1*03:01 and *15:01 in European [7,8], *15:03 in African-American , *08:02 in Hispanic  and *15:01 and *15:02 in Asian populations [11,12,13,14]. Gene dosage effects were not noted in the associations of HLA-DRB1 alleles with susceptibility to SLE in that homozygosity for a susceptibility allele does not confer higher disease risk than heterozygosity for that allele. However, only limited information is available concerning protective DRB1 alleles for SLE, i.e. those with a reduced frequency in patients. Here, we sought protective, as well as predispositional, HLA-DRB1 alleles in Japanese SLE patients. We also explored associations of DRB1 alleles with SLE phenotypes including the presence of autoanti- body and clinical manifestations of disease.
Abstract: Employment level and its fluctuations are historically one of the most discussed topics in the economic literature. This study focuses on the differences in employment’s sensitivity to the business cycle, existent between small and medium enterprises (SMEs) and large companies in the Portuguese economy. Which group of firms presents a more significant reduction in employment level during a recession? And during expansions? Are those SMEs with more fragile business or large firms with more employees? The theoretical discussion is still an open debate, being far from a consensus. The study analyses four major economic sectors - Construction, Retail Trade, Services and Industry between 2000 and 2012. The database is first used for this approach to the labor market and is developed by Statistics Portugal. Regarding the Portuguese economy for the sectors studied, the conclusions are clear, large firms are more sensitive to the economic cycle, regardless of their economic sector, recording more significant employment variations than SMEs. These conclusions call into question some well known ideas about SME’s contribution to the employment variations over the business cycle, opening the discussion on the determinants of these differences between SMEs and large companies’ performance.
$EVWUDFW5HODWLRQEHWZHHQFOLQLFDODQGDQWKURSRPHWULFGDWDDQGV\VWHPLFLQIODPPDWLRQLQSDWLHQWVZLWK&23' 3HUWVHYDɌȺ0\NKDLO\FKHQNR'6 Recently, much attention is devoted to systemic inflammationin patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to determine the relationship between clinical and anthropometric data with systemic inflammationin stable COPD patients. According to the study CRP levels were raised in 44% of patients (7.9 [7,1-10,9). Serum CRP was significantly higher in stable COPD patients than in control subjects (p=0.04). CRP correlated well with the pack/years index(p = 0,032) and disease duration (p=0,01). It wasn’t established linkbetween CRP levels and height, weight, stage, disease category. CRP level affected the frequency of exacerbations (r=0,50; p=0,01). Patients with high CRP level had significantly more exacerbations in the past year (p=0.01). Patients who received any type of therapy for a long period of time had lower CRP levels, than patients who did not reseive any therapy.