RAGs and Regulation of Autoantibodies

Autoreactive antibodies are etiologic agents in a number of autoimmune diseases. Like all other antibodies these antibodies are produced in developing B cells by V(D)J recombination in the bone marrow. Three mechanisms regulate autoreactive B cells: deletion, receptor editing, and anergy. Here we review the prevalence of autoantibodies in the initial antibody repertoire, their regulation by receptor editing, and the role of the recombinase proteins (RAG l and RAG2) in this process

Stratégies d'élimination de l'azote d'un effluent urbain dans un réacteur discontinu séquentiel (SBR)

Le traitement des effluents urbains par réacteurs discontinus séquentiels (SBR : Sequencing Batch Reactor) constitue une solution alternative aux traitements par systèmes à boue activée en effectuant le traitement du carbone, la séparation liquide solide et l'élimination des nutriments au sein d'un bassin unique grâce à une gestion adéquate des cycles temporels de réaction. L'alternance de phases aérées et anoxiques suivie d'une période de décantation conduit en théorie à l'élimination quasi totale des ions nitrate formés lors de la phase de nitrification aérobie. Cependant, selon la charge appliquée, le carbone totalement dégradé lors de la phase préliminaire d'aération ne peut servir de source de carbone pour la dénitrification exogène.Afin d'accélérer la dénitrification, plusieurs solutions sont possibles : l'une consiste à allonger la deuxième phase d'anoxie suffisamment longtemps pour traiter les ions nitrate résiduels au cours d'un processus de dénitrification endogène, l'autre à diminuer le temps de réaction aérobie tout en augmentant la fréquence des séquences aérobie/anoxie afin de conserver du carbone résiduel lors de la dénitrification. Une troisième solution réside dans l'ajout d'une source de carbone exogène suite à l'étape de nitrification de manière à permettre une assimilation plus rapide et plus efficace des ions nitrate formés (dénitrification exogène).L'article compare les résultats d'abattement sur le carbone et l'azote d'une eau usée urbaine en utilisant les trois types de fonctionnement. Il en résulte la définition d'une stratégie globale de contrôle du procédé, chacun des scénarii pouvant être privilégié en fonction de la qualité de l'effluent de départ et des contraintes de traitement.Wastewater treatment by a Sequencing Batch Reactor (SBR) provides an alternative solution to activated sludge treatment, by carrying out carbon treatment, liquid-solid separation and nutrient removal in a single tank, thanks to the appropriate management of the temporal reaction cycles. Alternating the aeration and anoxic phases, followed by a decantation period, leads, in theory, to the almost total removal of nitrate ions formed during the aerobic nitrification phase. However, depending on the applied load, the carbon that is totally degraded during the preliminary aeration phase, cannot be used as a source of carbon for exogenic denitrification.Several solutions are possible in order to accelerate denitrification: one consists of lengthening sufficiently the second anoxic phase to treat the residual nitrate ions during the endogenous denitrification process; another strategy involves reducing the aerobic reaction time, while increasing the frequency of aerobic/anoxic sequences in order to preserve residual carbon during denitrification. A third solution lies in the addition of a source of exogenic carbon after the nitrification stage, to allow a quicker and more efficient assimilation of the nitrate ions that are formed (exogenic denitrification). This article compares the results of reducing carbon and nitrogen in wastewater, using three types of operation.The cycle of reference has been established starting from previous bibliographical results (WUN JERN and DROSTE, 1989) and simulations using the model ASM1 (HENZE et al., 1986). It consists of an anoxic feeding, followed by an anoxic phase, then an aerobic phase and another anoxic phase. The cycle ends by the settling and decanting phases. The lengths of these different phases are: 1 h, 0.5 h, 4.5 h, 3.25 h, 1 h, 1 h. This reference cycle, carried out at the laboratory, leads to the elimination of 90% of the Chemical Oxygen Demand (COD), 95% of the Biological Oxygen Demand (BOD5) and more than 80% of total nitrogen, i.e. with residual concentrations of 60 mg×L-1 for the Dissolved Organic Carbon (DOC), 5 mg×L-1 for the Biological Oxygen Demand, and 10 mg×L-1 for total nitrogen. These results are comparable with those in the literature (IRVINE et al., 1987, MELCER et al., 1987, YANG et al., 1999).The results obtained during the reference cycle enabled us to reach a rate of total nitrogen removal of 85% and a global nitrogen concentration in the effluent of 11 mg×L-1. Nitrification and denitrification rates yielded values of 0.8 mg N-NH4+×gMVS-1 ×h-1 and 0.8 mg N-NO3 -×gMVS-1×h-1 respectively. Total nitrogen removal was not completely achieved because of the lack of available carbon. This lack of carbon favours endogenic denitrification, characterized by a slow denitrification rate 0.8 mg N-NO3 -×mgMVS-1×h-1, compared to exogenic denitrification characterized by a higher nitrogen reduction rate (about 2 mg N-NO3 -×mgMVS-1 ×h-1). This fact was experimentally confirmed with carbon addition in the form of acetate at the beginning of the second anoxic phase. In this case, carbon addition significantly improves the denitrification rate compared to the same experiment without exogenic carbon addition: 2 mg N-NO3 -×mgMVS-1 ×h-1 versus 0.8 mg N-NO3 -×mgMVS-1 ×h-1. However, this method raises operating costs for the process.In order to reach complete nitrogen removal without the addition of synthetic carbon, it is possible to increase the anoxic phase time scale from 3 hours to 15 hours. Although the results in term of carbon and nitrogen removal are satisfactory when the anoxia phase is lengthened, the concentration in the discharged effluent is 0.33 mg total N×L-1, and thus this technique decreases the productivity of the SBR. The feeding cycles of a biological reactor being variable, a regulation based on the use of the evolution of the pH, or the redox potential, can be considered (PAVELJ et al., 2001; ANDREOTTOLA et al., 2001). This regulation would make it possible to adapt the duration of the phases of anoxia to the necessary treatment.To overcome this drawback, a possible approach consists in replacing the aerobic / anoxic phase in the reference cycle by five aerobic / anoxic phases during the same time. Unfortunately, this method leads to a decrease in nitrogen removal and in the nitrification rate, compared to classical cycle (65% versus 85%, and 0.4 mg N-NO3 - ×mgMVS-1 ×h-1 versus 0.8 mg N-NO3 -×mgMVS-1 ×h-1, respectively). The nitrification rate is, in this case, half that obtained in the reference cycle, probably due to delays related to the induction of nitrification and denitrification. This strategy, consisting of increasing the aeration / no aeration frequency, has to be optimized in term of nitrification and denitrification ratios.A better solution from the economic and productivity points of view is the addition of wastewater at the beginning of anoxic phase. This strategy implies the modification of the cycle. First, after the anoxic feeding, an aerobic phase allows carbon and nitrogen oxidation. In order to supply an available carbon source for exogenic denitrifcation, a second feeding is introduced at the beginning of the second anoxic phase. This addition also contains ammonium ions and implies new nitrification and denitrification steps. This last denitrification phase is then endogenic.Carbon addition in the form of wastewater leads to an improvement in nitrogen removal. The exogenic denitrification rate is twice the value for endogenous denitrification for the same cycle of operation (1.6 mg N-NO3 -×gMVS-1 ×h-1 versus 0.9 mg N-NO3 -×gMVS-1 ×h-1 respectively). This strategy yields a final concentration of 3 mg N×L-1 and the nitrification and denitrification rates are similar to those of the traditional processes.In conclusion, the addition of synthetic carbon in the form of acetate must be preserved as a means of acting quickly in the event of dysfunction (that can be detected by monitoring the redox potential or the pH), although this technique significantly increases the cost of operation. Although the best economic solution to improve denitrification is carbon addition in the form of wastewater, other strategies can be undertaken according to the goals of the treatment process. When the wastewater load is sufficiently weak (night period), the endogenous phase of denitrification can be lengthened. In the event of an important load, carbon addition (in synthetic form or as waste water) makes it possible to eliminate the nitrate ions exogenically

Consequences of paternally inherited effects on the genetic evaluation of maternal effects

Background: Mixed models are commonly used for the estimation of variance components and genetic evaluation of livestock populations. Some evaluation models include two types of additive genetic effects, direct and maternal. Estimates of variance components obtained with models that account for maternal effects have been the subject of a long-standing controversy about strong negative estimates of the covariance between direct and maternal effects. Genomic imprinting is known to be in some cases statistically confounded with maternal effects. In this study, we analysed the consequences of ignoring paternally inherited effects on the partitioning of genetic variance. Results: We showed that the existence of paternal parent-of-origin effects can bias the estimation of variance components when maternal effects are included in the evaluation model. Specifically, we demonstrated that adding a constraint on the genetic parameters of a maternal model resulted in correlations between relatives that were the same as those obtained with a model that fits only paternally inherited effects for most pairs of individuals, as in livestock pedigrees. The main consequence is an upward bias in the estimates of the direct and maternal additive genetic variances and a downward bias in the direct-maternal genetic covariance. This was confirmed by a simulation study that investigated five scenarios, with the trait affected by (1) only additive genetic effects, (2) only paternally inherited effects, (3) additive genetic and paternally inherited effects, (4) direct and maternal additive genetic effects and (5) direct and maternal additive genetic plus paternally inherited effects. For each scenario, the existence of a paternally inherited effect not accounted for by the estimation model resulted in a partitioning of the genetic variance according to the predicted pattern. In addition, a model comparison test confirmed that direct and maternal additive models and paternally inherited models provided an equivalent fit. Conclusions: Ignoring paternally inherited effects in the maternal models for genetic evaluation can lead to a specific pattern of bias in variance component estimates, which may account for the unexpectedly strong negative direct-maternal genetic correlations that are typically reported in the literature

Elimination de l'azote et du phosphore dans un lagunage à haut rendement

L'objectif de cette étude est de comprendre le fonctionnement épuratoire de l'écosystème particulier que constitue le lagunage à haut rendement (LHR) afin de déterminer les principaux facteurs responsables de l'élimination de l'azote et du phosphore.Sur un bassin de 48 m2, alimenté eu eaux usées domestiques préalablement traitées pendant une semaine dans un bassin primaire ont été suivies selon un rythme hebdomadaire les formes carbonées, azotées et phosphorées dis-soutes et particulaires, les variables caractéristiques de l'activité photosynthétiques (chlorophylle a, pH et 02) et les données climatiques (rayonnement solaire et température). Une analyse en composantes principales réalisée sur l'ensemble des résultats a montré, d'une part l'opposition des variables climatiques et photosynthétiques aux formes minérales de l'azote et du phosphore (N-NH4 et P-PO4) et d'autre part l'influence de la charge organique sur le fonctionnement du système.L'évolution des formes azotées et phosphorées présente un effet saisonnier marqué. En hiver ou lors de surcharge organique importante, une augmentation du temps de séjour peut améliorer les rendements épuratoires. L'évolution de la matière organique dissoute est indépendante du cycle saisonnier. Au cours des deux années du suivi on observe une adaptation progressive de l'écosystème à la dégradation de la matière organique.Dans le lagunage à haut rendement l'élimination de l'azote et du phosphore est liée principalement à l'activité algale, qui entraîne une assimilation biologique et une élévation du pH, responsables des phénomènes chimiques de volatilisation de l'azote ammoniacal et de précipitation de phosphate de calcium.High rait algal ponds (HRAP) for wastewater treatment have been the locus of a lot of attention since their creation by Professor W.J. OSWALD in the early 1960' s. These aquatic ecosystems are hypereutrophic because of massive nutrient introduction with the wastewater influent. This kind of pond is very different from oxidation ponds because al short residence times (2 to 12 days), shallow depths (0.30 to 0.60 m) and constant mechanical mixing which improves algal growth.This study has been carried out in a small town in the department of Herault (France). The objective is to establish the efficiencies and mechanisms for nitrogen and phosphorus remval from secondary domestic wastewater by treatment by HRAP. A high rate algal pond of 48 m2 surface area and 35 cm depth, constantly mixed with paddle wheels was studied (fig. 1). Residence limes changed from 2 te 12 days with solar radiations and influent loading. The samples were collected once a week from the in- and outflow at 3 p.m. - Dissolved and particulate COD, varions nitrogen and phosphorus compounds, suspended solide, chlorophyll-a, pH, dissolved oxygen, temperature and irradiation were determined.The results of principal component analysis show a negative correlation between (1) the climatic and photosynthetic parameters and (2) inorganic nitrogen and phosphorus compounds, as well as the influence of organic loading on the HRAP efficiency.The chronological clustering analysis was performed on the data taking into account the discontinuities of effluent autrient contents (fig. 4). During the first year, from February to September 1988, good climatic conditions were shown to favour photosynthetic activity and consequently a good ammonia and orthophosphate removal. Front September 1988 to February 1989, the effluent was characterized by high ammonia and orthophosphate levels because of unfavourable climatic conditions and low photosynthetic activity. During the second year, the objective was to improve removal efficiencies ; the residence time was changed with solar radiations and influent loading. The results of the chronological clustering analysis of ammonia and orthophosphate levels showed only one sequence (February 1989-January1990) because the seasonal variations of nutrient removal were attenuated. The optimal residence time was found to be 4 days in summer and 12 days in winter.The evolution of dissolved chemical oxygen demand is independent of seasonal conditions but decreases with the maturity of the system (< 50 mg . l-1).The mass balance of nitrogen and phosphorus compounds has been established (fig. 5). In high rate algal pond influent, the main nitrogen form is ammonia. In the effluent the main nitrogen form is suspended organic nitrogen. The oxidized forms (NO2- et NO3) present very low levels ; nitrification is a minor process in the system. Ammonia is reduced by both assimilation and stripping ; suspended organic nitrogen in the effluent is an indicator of assimilation by algal biomass and loss of nitrogen is an indicator of ammonia stripping. With regard to directive 91/271 EEC concerning domestic wastewater treatment, partial algal separation is necessary in order to achieve 15 mg • l-1 total nitrogen, which is the limit for zones sensitive to eutrophication.The residual phosphate levels are controlled by pH, which is responsible for instantaneous calcium phosphate precipitation. As the dissolved calcium concentrations are high in the calcareous region near the site (Ca = 125 mg • l-1), the pH of the water will be the main contraint on phosphate elimination in the HRAP. Theoretical calculations indicate that the precipitate is probably an amorphous tricalcium phosphate in pseudoequilibrium (fig.6). Phosphate concentrations are much higher titan the values expected for calcium hydroxyapatite in equilibrium (MOUTIN et al., 1992). The limit of 2 mg • l-1 for phosphores can only be attained when pH reaches or exceeds 9.Nitrogen and phosphorus removal is correlated mainly with phytoplanktonic activity, which controls biological nutrients assimilation and pH levels. High pH values are responsable for ammonia stripping and calcium phosphate precipitation

Stress and Growth in Cancer: Mechanisms and Psychotherapeutic Interventions to Facilitate a Constructive Balance

Post-traumatic stress and growth are common responses to adverse life events such as cancer. In this article, we establish how cancer becomes a "fertile land" for the emergence of stress and growth responses and analyze the main mechanisms involved. Stress-growth responses on adjusting to cancer is potentially determined by factors like the phase of the illness (e.g., initial phases vs. period of survivorship), patient's coping strategies, meaning-making, and relationships with significant others. We also review the mechanisms of constructive and adaptative stress-growth balances in cancer to study the predictors, interrelated associations, triggering mechanisms, long-term results, and specific trajectories of these two responses to cancer. Finally, we update the evidence on the role of these stress-growth associations in psychologically adjusting to cancer. Together with this evidence, we summarize preliminary results regarding the efficacy of psychotherapeutic interventions that aim to facilitate a constructive psychological balance between stress and growth in cancer patients. Recommendations for future research and gaps in knowledge on stress-growth processes in this illness are also highlighted. Researchers are encouraged to design and use psychotherapeutic interventions according to the dynamic and changeable patients' sources of stress and growth along the illness. Relevant insights are proposed to understand the inconsistency of stress-growth literature and to promote psychotherapeutic interventions to facilitate a constructive balance between these key responses in cancer

Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes.

Pharmaceuticals are found in the aquatic environment but their potential effects on non-target species like fish remain unknown. This in vitro study is a first approach in the toxicity assessment of human drugs on fish. Nine pharmaceuticals were tested on two fish hepatocyte models: primary cultures of rainbow trout hepatocytes (PRTH) and PLHC-1 fish cell line. Cell viability, interaction with cytochrome P450 1A (CYP1A) enzyme and oxidative stress were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide tetrazolium (MTT), 7-ethoxyresorufin-o-deethylase (EROD) and dichlorofluorescein (DCFH-DA) assays, respectively. The tested drugs were clofibrate (CF), fenofibrate (FF), carbamazepine (CBZ), fluoxetine (FX), diclofenac (DiCF), propranolol (POH), sulfamethoxazole (SFX), amoxicillin (AMX) and gadolinium chloride (GdCl(3)). All substances were cytotoxic, except AMX at concentration up to 500 microM. The calculated MTT EC(50) values ranged from 2 microM (CF) to 651 microM (CBZ) in PLHC-1, and from 53 microM (FF) to 962 microM (GdCl(3)) in PRTH. CF, FF, and FX were the most cytotoxic drugs and induced oxidative stress before being cytotoxic. Compared to hepatocytes from human and dog, fish hepatocytes seemed to be more susceptible to the peroxisome proliferators (PPs) CF and FF. In PLHC-1 cells none of the tested drugs induced the EROD activity whereas POH appeared as a weak EROD inducer in PRTH. Moreover, in PRTH, SFX, DiCF, CBZ and to a lesser extend, FF and CF inhibited the basal EROD activity at clearly sublethal concentrations which may be of concern at the biological and chemical levels in a multipollution context

Challenging Methods and Results Obtained from User-Generated Content in Barcelona’s Public Open Spaces

User-generated content (UGC) provides useful resources for academics, technicians and policymakers to obtain and analyse results in order to improve lives of individuals in urban settings. User-generated content comes from people who voluntarily contribute data, information, or media that then appears in a way which can be viewed by others; usually on the Web. However, to date little is known about how complex methodologies for getting results are subject to methodology-formation errors, personal data protection, and reliability of outcomes. Different researches have been approaching to inquire big data methods for a better understanding of social groups for planners and economic needs. In this chapter, through UGC from Tweets of users located in Barcelona, we present different research experiments. Data collection is based on the use of REST API; while analysis and representation of UGC follow different ways of processing and providing a plurality of information. The first objective is to study the results at a different geographical scale, Barcelona’s Metropolitan Area and at two Public Open Spaces (POS) in Barcelona, Enric Granados Street and the area around the Fòrum de les Cultures; during similar days in two periods of time - in January of 2015 and 2017. The second objective is intended to better understand how different types of POS’ Twitter-users draw urban patterns. The Origin-Destination patterns generated illustrate new social behaviours, addressed to multifunctional uses. This chapter aims to be influential in the use of UGC analysis for planning purposes and to increase quality of life

Genetic analysis of rennet coagulation time, curd-firming rate, and curd firmness assessed over an extended testing period using mechanical and near-infrared instruments

Abstract The aims of this study were (1) to analyze rennet coagulation time (RCT), curd-firming rate, and curd firmness obtained by extending the standard 30-min testing time to 45min; (2) to estimate heritabilities of the aforementioned traits determined by mechanical (Formagraph; Foss Electric, Hillerod, Denmark) and near-infrared optical (Optigraph; Ysebaert, Frepillon, France) instruments, and to assess the statistical relevance of their genetic background by using the Bayes factor procedure, the deviance information criterion, and the mean squared error; (3) to estimate phenotypic and genetic relationships between instruments within trait and between traits within instrument; and (4) to obtain correlations for sire rankings based on the used instruments. Individual milk samples were collected from 913 Brown Swiss cows reared in 63 herds located in Trento Province (Italy). Milk coagulation properties (MCP) were measured using 2 different instruments: Formagraph and Optigraph. Both instruments were housed in the same laboratory and operated by the same technician. Each sample was analyzed simultaneously on each instrument. All experimental conditions (milk temperature and the concentration and type of rennet) were identical. For the analysis, univariate and bivariate animal models were implemented using Bayesian methods. Univariate analyses were conducted to test the hypothesis that the traits showed additive genetic determination. Deviance information criterion, Bayes factor, and mean squared error were used as model choice criteria. The main results were that (1) RCT could be measured on all samples by extending the observation time to 45min, and its genetic parameters ( h 2 =0.23) and breeding values could be estimated while avoiding the bias of noncoagulating samples; (2) curd-firming rate could be measured on almost all milk samples, and its genetic parameters could be estimated for the first time on a field data set ( h 2 =0.21); (3) for the first time, genetic parameters of curd firmness 45min after rennet addition ( h 2 =0.12) were estimated, and they were compared with curd firmness 30min after rennet addition ( h 2 =0.17); and (4) MCP estimated using the Optigraph appeared to be genetically different from those determined by Formagraph, with the partial exception of RCT (genetic correlation=0.97). Breeding strategies for the improvement of MCP must be planned with caution. Currently, the high throughput, ease of use, and reduced costs of analysis make predictions obtained from mid-infrared spectroscopy (MIRS) on untreated milk samples a promising alternative to produce relevant data at the population level. The use of mechanical lactodynamographs to establish reference data for MIRS calibrations have been already studied, whereas the use of near-infrared optical lactodynamographs as a reference method for MIRS calibrations needs to be investigated

Characterisation of activated sludge by automated image analysis : validation on full-scale plants

Automated methods based on the analysis of macro- and meso-scale images has been developed to characterise activated sludge in terms of size and shape (fractal dimension) of flocs and abundance of filamentous bacteria. After tests on pilot-scale reactors, the method has been validated on full-scale samples from twelve different wastewater treatment plants in France and Portugal

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed