Effect of testosterone and fluoxetine on aggressive behaviors of fighting fish, Betta splendens

Effects of oral administration of testosterone and fluoxetine exposure on aggressive behavior of the fighting fish, Betta splendens, were investigated. Testosterone diluted in ethanol and sprayed on pre-weighted pellet to achieve concentrations of 0, 1, 2 and 4 mg/kg of hormone in food. Two main behaviors were recorded: the time in front of mirror and duration of the gill flaring using a mirror 8 and 15 days after the start of the experiment. Then, half of the specimens in each treatment subjected to waterborne fluoxetine at a concentration of 100 µg/L for 24 hours and the behavior was recorded. After 8 days of feeding, the time in front of mirror and duration of gill flaring were not significantly different between the treatments. Duration of the gill flaring increased significantly after 15 days; however there was no significant difference for the behavior in front of the mirror. Over time the aggressive behaviors were reduced significantly after fluoxetine exposure. This study indicated that fluoxetine in the aquatic environment alters the aggressive behaviors of the fighting fish

Adaptive Frequency Hopping Algorithms for Multicast Rendezvous in DSA Networks

Abstract-Establishing communications in a dynamic spectrum access (DSA) network requires communicating nodes to "rendezvous" before transmitting their data packets. Frequency hopping (FH) provides an effective method for rendezvousing without relying on a predetermined control channel. FH rendezvous protocols have mainly targeted pairwise rendezvous, using fixed (non-adaptive) FH sequences and assuming a homogeneous spectrum environment, i.e., all nodes perceive the same spectrum opportunities. In this paper, we address these limitations by developing three multicast rendezvous algorithms: AMQFH, CMQFH, and nested-CMQFH. The three algorithms are intended for asynchronous spectrum-heterogeneous DSA networks. They provide different tradeoffs between speed and robustness to node compromise. We use the uniform k-arbiter and the Chinese remainder theorem (CRT) quorum systems to design our multicast rendezvous algorithms. We also design two "optimal" channel ordering mechanisms for channel sensing and assignment, one for AMQFH and the other for CMQFH and nested-CMQFH. Finally, we develop a proactive out-of-band sensing based dynamic FH (DFH) algorithm for online adaptation of the FH sequences used in the proposed rendezvous algorithms. Extensive simulations are used to evaluate our algorithms

Serum PlGF and EGF are independent prognostic markers in non-metastatic colorectal cancer

The aim of this study was to determine the prognostic value of circulating angiogenic cytokines in non-metastatic colorectal cancer (CRC) patients. Preoperative serum samples of a training (TC) (n = 219) and a validation cohort (VC) (n = 168) were analyzed via ELISA to determine PlGF, EGF, VEGF, Ang1, PDGF-A, PDGF-B, IL-8 and bFGF levels. In addition, survival was correlated with PlGF and EGF expression measured by microarray and RNAseq in two publicly available, independent cohorts (n = 550 and n = 463, respectively). Prognostic values for overall (OS) and disease-free survival (DFS) were determined using uni- and multivariate Cox proportional hazard analyses. Elevated PlGF is predictive for impaired OS (TC: HR 1.056; p = 0.046; VC: HR 1.093; p = 0.001) and DFS (TC: HR 1.052; p = 0.029; VC: HR 1.091; p = 0.009). Conversely, elevated EGF is associated with favorable DFS (TC: HR 0.998; p = 0.045; VC: HR 0.998; p = 0.018) but not OS (TC: p = 0.201; VC: p = 0.453). None of the other angiogenic cytokines correlated with prognosis. The prognostic value of PlGF (OS + DFS) and EGF (DFS) was confirmed in both independent retrospective cohorts. Serum PlGF and EGF may serve as prognostic markers in non-metastatic CRC

Intestinal B cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling

BACKGROUND & AIMS: The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC. METHODS: C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans. RESULTS: Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis. CONCLUSIONS: Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH. IMPACT AND IMPLICATIONS: There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis

Intestinal BMP-9 locally upregulates FGF19 and is down-regulated in obese patients with diabetes

believed to be mainly produced in the liver. The serum levels of BMP-9 were reported to be reduced in newly diagnosed diabetic patients and BMP-9 overexpression ameliorated steatosis in the high fat diet-induced obesity mouse model. Furthermore, injection of BMP-9 in mice enhanced expression of fibroblast growth factor (FGF)21. However, whether BMP-9 also regulates the expression of the related FGF19 is not clear. Because both FGF21 and 19 were described to protect the liver from steatosis, we have further investigated the role of BMP-9 in this context. We first analyzed BMP-9 levels in the serum of streptozotocin (STZ)-induced diabetic rats (a model of type I diabetes) and confirmed that BMP-9 serum levels decrease during diabetes. Microarray analyses of RNA samples from hepatic and intestinal tissue from BMP-9 KO- and wild-type mice (C57/Bl6 background) pointed to basal expression of BMP-9 in both organs and revealed a down-regulation of hepatic Fgf21 and intestinal Fgf19 in the KO mice. Next, we analyzed BMP-9 levels in a cohort of obese patients with or without diabetes. Serum BMP-9 levels did not correlate with diabetes, but hepatic BMP-9 mRNA expression negatively correlated with steatosis in those patients that did not yet develop diabetes. Likewise, hepatic BMP-9 expression also negatively correlated with serum LPS levels. In situ hybridization analyses confirmed intestinal BMP-9 expression. Intestinal (but not hepatic) BMP-9 mRNA levels were decreased with diabetes and positively correlated with intestinal E-Cadherin expression. In vitro studies using organoids demonstrated that BMP-9 directly induces FGF19 in gut but not hepatocyte organoids, whereas no evidence of a direct induction of hepatic FGF21 by BMP-9 was found. Consistent with the in vitro data, a correlation between intestinal BMP-9 and FGF19 mRNA expression was seen in the patients’ samples. In summary, our data confirm that BMP-9 is involved in diabetes development in humans and in the control of the FGF-axis. More importantly, our data imply that not only hepatic but also intestinal BMP-9 associates with diabetes and steatosis development and controls FGF19 expression. The data support the conclusion that increased levels of BMP-9 would most likely be beneficial under pre-steatotic conditions, making supplementation of BMP-9 an interesting new approach for future therapies aiming at prevention of the development of a metabolic syndrome and liver steatosis

Intestinal B-cells license metabolic T-cell activation in NASH microbiota/antigen-independently and contribute to fibrosis by IgA-FcR signalling

BACKGROUND & AIMS The progression of nonalcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC. METHODS C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH diets (for example, choline-deficient high-fat diet, CD-HFD) or chow diet for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a CD-HFD, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with NAFL, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and scRNA-Seq analysis were performed in liver and gastrointestinal tissue for immune cells in mice and humans. RESULTS Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen-specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B-cells and showed a positive correlation between IgA levels and activated FcRγ+ hepatic myeloid cells as well extent of liver fibrosis. CONCLUSIONS Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for treating NASH. IMPACT AND IMPLICATIONS Nonalcoholic steatohepatitis (NASH) is a chronic inflammatory condition on the rise and can lead to hepatocellular carcinoma (HCC), the 3rd most common cause of cancer-related death worldwide. Currently, there is no effective treatment for this progressive disease that correlates with a marked risk of HCC mortality and carries a substantial healthcare burden. To date, among all the solid tumours, especially in HCC, the incidence and mortality rates are almost the same, making it crucial to find curative treatments for chronic diseases, such as NASH, which highly predispose to tumorigenesis. We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we could show that the absence of B cells prevented HCC development. B-cell intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets in combinatorial NASH therapies against inflammation and fibrosis

Intellectuals and Idea of Human Rights (with Emphasis on the Second Pahlavi Era)

“Human rights” is one of the most important achievements of western civilization which could affect the internal law of many countries. In spite of the fact that some states have used human rights as a means of furthering their own interests undermining its ethical function, these rights have been formulated to respect “human dignity”. This paper tries to answer two questions: what is the relationship between intellectuals and the idea of human rights? And the second and main question is that in the second Pahlavi era what were the religious intellectual explanations of human rights? The answer to the first question is that intellectuals were among the most significant social forces who were always concerned with implementing human rights. The answer to the second is that in the second Pahlavi era, religious intellectuals were trying to draw the concepts of human rights from the traditional sources, develop and employ them against the reign of Pahlavi. e government extended to include the responsibilities of the business community and the civil society. ‘Good governance’ is more idealistic form of governance that administers public affairs and resources with utmost transparency and attention to different dimensions of human rights, as civil, cultural, economic, political and social rights. حقوق بشر یکی از مهم‌ترین دستاوردهای تمدن غرب محسوب می‌گردد و طی چند دهه‌ اخیر نفوذ بسیاری در کشورهای جهان داشته و توانسته بر حقوق داخلی آنها تأثیرگذار باشد. اگرچه این حقوق در دست عده‌ای به عنوان حربه برای پیشبرد منافع‌شان به کار می‌رود و بدین ترتیب کارکرد اخلاقی خود را از دست می‌دهد و عده‌ای نیز بنا به دلایلی آن‌را صرفاً در حد یک آرمان تحقق‌ناپذیر تلقی می‌کنند اما با این حال باید گفت، این مجموعه قوانین به نیت انسانی و به قصد احترام به «کرامت انسان» تدوین شده‌ و در برخی موارد توانسته تا حدودی مثمر ثمر واقع شود. این مقاله در صدد پاسخگویی به دو سؤال بر می‌آید. اول آنکه چه ارتباطی میان روشنفکران و ایده‌ حقوق بشر وجود دارد؟ به عبارتی حقوق بشر چه اهمیت و جایگاهی برای روشنفکران دارد؟ و سؤال دوم که مرتبط با جامعه ایران دوران پهلوی دوم می‌باشد این است که روشنفکران دینی در این دوران، چه تعبیری از مفاهیم حقوق بشری داشتند و چطور از آنها استفاده می‌کردند؟ در پاسخ به سؤال نخست، فرضیه‌‌ ما آن است که روشنفکران به عنوان مهم‌ترین قشر در هر جامعه‌ای تلقی می‌شوند که دغدغه‌ برقراری ایده‌ حقوق بشر را دارند؛ چرا که اغلب در آراء و افکارشان به مفاهیم اخلاقی و حقوق بشری توجه داشته‌اند. فرضیه‌ای که در پاسخ به سؤال دوم ارائه می‌شود آن است که در این دوران (پهلوی دوم) متفکران و روشنفکران دینی سعی داشته‌اند مفاهیم حقوق بشری را از منابع سنتی استخراج کنند، آنها را بپرورند و در راستای مبارزه با رژیم مورد نظر به کار ببرند

Modeling a Multi-Objective Green Inventory-Routing Problem with Transshipment Option

International audienceThis paper addresses a multi-period inventory routing problem (IRP) where capacitated vehicles distribute products from multiple suppliers to one retailer to meet the given demand of products. The demand associated with retailer is assumed to be time varying and deterministic. Greenhouse gases emission is a major concern globally since they are key players in global warming. Routing decisions can help in the reduction of Greenhouse gases emissions if these emissions are taken into account by the decision makers. Also, the transshipment option as one of the main topics of this paper is considered in the proposed model. The transshipment option is one of the most recent things that can be considered today in supply chain management. This option makes the vehicle meet the required product of a node directly from the product supplier's node or from a node previously stored in a product temporarily. As a result, it reduces greenhouse gases and costs by reducing the distance traveled. The proposed model is a mixed-integer linear program that coded and solved in GAMS. We provide a numerical study showing the applicability of the model

Effect of testosterone and fluoxetine on aggressive behaviors of fighting fish, Betta splendens

Effects of oral administration of testosterone and fluoxetine exposure on aggressive behavior of the fighting fish, Betta splendens, were investigated. Testosterone diluted in ethanol and sprayed on pre-weighted pellet to achieve concentrations of 0, 1, 2 and 4 mg/kg of hormone in food. Two main behaviors were recorded: the time in front of mirror and duration of the gill flaring using a mirror 8 and 15 days after the start of the experiment. Then, half of the specimens in each treatment subjected to waterborne fluoxetine at a concentration of 100 µg/L for 24 hours and the behavior was recorded. After 8 days of feeding, the time in front of mirror and duration of gill flaring were not significantly different between the treatments. Duration of the gill flaring increased significantly after 15 days; however there was no significant difference for the behavior in front of the mirror. Over time the aggressive behaviors were reduced significantly after fluoxetine exposure. This study indicated that fluoxetine in the aquatic environment alters the aggressive behaviors of the fighting fish

Etiology and short-term outcome of children with convulsive status epilepticus admitted to Tabriz Children’s Hospital, Iran

Introduction: Status epilepticus (SE) are associated with high rates of morbidity and mortality, yet early diagnosis and treatment will improve patients’ outcome. This study was carried out to determine etiology, and early-outcome of our overall management of pediatric SE in patients admitted to Tabriz Children’s Hospital, Iran. Methods: In this cross-sectional and analytical study from January 2013 to January 2014, 43 patients with SE under the age of 15 years were enrolled. Demographic characteristics, etiology and outcome of every patient were recorded. SPSS for Windows software was used for statistical analysis. P-value of less than 0.05 was considered to be statistically significant in all comparisons. Results: The highest rate of SE was happened in age-subgroup of 1-5 years. The two most common causes of SE in our patients were remote symptomatic (55.8%) and prolonged febrile convulsions (20.9%). Refractory SE (RSE) was detected in 15 (34.8%) patients. Poor early-outcome was shown in 8 (18.6%) patients (4 mortalities and 4 morbidities) of whom 5 (33.3%) had RSE, and 3 (10.7%) from SE group (P = 0.010). Young age was a risk factor for mortality (P = 0.010). Recurrent SE was occurred in 3 (7.0%) of patients. Conclusion: Early-outcome of SE in children is mainly determined by age and underlying disorder