•Rate of phosphate removal by electrocoagulation is governed by precipitation of AlPO4(s) and/or adsorption on Al(OH)3.•Kinetics of phosphate removal is depending only on electrical charge whatever ...the time of treatment and the current density.•Electrical consumption is lower at low current density because of the limited ohmic voltage drop.•pH variation depends on production of OH- at the cathode and its reaction with Al3+.
Treatment of water containing phosphate by electrocoagulation has been studied in a laboratory batch reactor. The effect of operating parameters on both phosphate removal efficiency and pH evolution has been investigated. Influence of distance between electrodes, current density, initial pH, temperature and conductivity has been extensively studied in a wide range of values. The results show that the removal efficiency depends on the electrical charges; the same efficiency is obtained with low current density with long time of treatment, or higher current intensity with short treatment time. The time evolution of the pH during the treatment strongly depends on the operating conditions but the final pH is more or less the same due to the buffering effect of Al(OH)3/Al(OH)4- mixture. Effects of the temperature, often disregarded in the literature shows that treatment rate is strongly increased with temperature whereas conductivity near 1mS/cm is enough to ensure reasonable treatment rate. The electrical energy consumption (around 4Kw/m3) is acceptable to achieve 90% of conversion but lower current density is preferable because of the lower voltage drop.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The outcome of patients with resistant phenotypes of acute lymphoblastic leukemia (ALL) or those who relapse remains poor. We investigated the mechanism of cell death induced by metformin in Bp- and ...T-ALL cell models and primary cells, and show that metformin effectively induces apoptosis in ALL cells. Metformin activated AMPK, down-regulated the unfolded protein response (UPR) demonstrated by significant decrease in the main UPR regulator GRP78, and led to UPR-mediated cell death via up-regulation of the ER stress/UPR cell death mediators IRE1α and CHOP. Using shRNA, we demonstrate that metformin-induced apoptosis is AMPK-dependent since AMPK knock-down rescued ALL cells, which correlated with down-regulation of IRE1α and CHOP and restoration of the UPR/GRP78 function. Additionally rapamycin, a known inhibitor of mTOR-dependent protein synthesis, rescued cells from metformin-induced apoptosis and down-regulated CHOP expression. Finally, metformin induced PIM-2 kinase activity and co-treatment of ALL cells with a PIM-1/2 kinase inhibitor plus metformin synergistically increased cell death, suggesting a buffering role for PIM-2 in metformin's cytotoxicity. Similar synergism was seen with agents targeting Akt in combination with metformin, supporting our original postulate that AMPK and Akt exert opposite regulatory roles on UPR activity in ALL. Taken together, our data indicate that metformin induces ALL cell death by triggering ER and proteotoxic stress and simultaneously down-regulating the physiologic UPR response responsible for effectively buffering proteotoxic stress. Our findings provide evidence for a role of metformin in ALL therapy and support strategies targeting synthetic lethal interactions with Akt and PIM kinases as suitable for future consideration for clinical translation in ALL.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction Le développement de nouvelles stratégies thérapeutiques pour prévenir et traiter l'obésité se situe au cœur d'une problématique de santé publique, largement relayée par les médias au ...sein de notre société. La fonction barrière de l'intestin est altérée au cours de l'obésité et pourrait favoriser le développement de l'endotoxémie de faible amplitude responsable du phénomène inflammatoire corrélé au développement de l'adiposité. Des altérations de la barrière intestinale ont été démontrées dans différents modèles animaux d'obésité. Notre objectif est de définir la contribution de l'AMPK dans la formation et la stabilisation des jonctions serrées au niveau de l'épithélium intestinal. Matériels et Méthodes Pour étudier le rôle physiologique de l'AMPK dans l'intestin, des animaux invalidés spécifiquement de l'AMPK dans les cellules épithéliales de l'intestin (AMPKalpha1fl/fl/alpha2fl/fl ; Villin-Cre ou Villin-Cre-AMPK) ont été généré. La perméabilité intestinale a été mesurée in vivo et in vitro sur des segments d'intestin en chambre de Ussing. Résultats Les souris Villin-Cre-AMPK ne présentent aucun défaut de poids corporel, de la prise alimentaire, du transit gastro-intestinal ou de la longueur de l'intestin. Bien qu'aucune altération histologique et modification de l'expression de la protéine des jonctions serrées ZO-1 n'ait été observée, l'absence de l'AMPK provoque une augmentation de la perméabilité intestinale in vivo, indiquant un défaut de la barrière intestinale. Des études de perméabillté réalisées ex vivo ont permis de montrer une augmentation de la perméabilité paracellulaire restreinte au jéjunum et au colon distal. La perméabilité transcellulaire est également accrue dans le colon distal des souris Villin-Cre-AMPK. Conclusions Nos résultats mettent en évidence l'importance de l'AMPK dans la régulation de l'homéostasie de la barrière intestinale et suggèrent que l'AMPK pourrait constituer une cible thérapeutique de choix pour limiter les déficits de la barrière intestinale au cours de l'obésité.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Bacteriophage (phage) are bacterial predators that can also spread antimicrobial resistance (AMR) genes between bacteria by generalised transduction. Phage are often present alongside antibiotics in ...the environment, yet evidence of their joint killing effect on bacteria is conflicted, and the dynamics of transduction in such systems are unknown. Here, we combine in vitro data and mathematical modelling to identify conditions where phage and antibiotics act in synergy to remove bacteria or drive AMR evolution. We adapt a published model of phage-bacteria dynamics, including transduction, to add the pharmacodynamics of erythromycin and tetracycline, parameterised from new in vitro data. We simulate a system where two strains of Staphylococcus aureus are present at stationary phase, each carrying either an erythromycin or tetracycline resistance gene, and where multidrug-resistant bacteria can be generated by transduction only. We determine rates of bacterial clearance and multidrug-resistant bacteria appearance, when either or both antibiotics and phage are present at varying timings and concentrations. Although phage and antibiotics act in synergy to kill bacteria, by reducing bacterial growth antibiotics reduce phage production. A low concentration of phage introduced shortly after antibiotics fails to replicate and exert a strong killing pressure on bacteria, instead generating multidrug-resistant bacteria by transduction which are then selected for by the antibiotics. Multidrug-resistant bacteria numbers were highest when antibiotics and phage were introduced simultaneously. The interaction between phage and antibiotics leads to a trade-off between a slower clearing rate of bacteria (if antibiotics are added before phage), and a higher risk of multidrug-resistance evolution (if phage are added before antibiotics), exacerbated by low concentrations of phage or antibiotics. Our results form hypotheses to guide future experimental and clinical work on the impact of phage on AMR evolution, notably for studies of phage therapy which should investigate varying timings and concentrations of phage and antibiotics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper deals with the efficiency of electrocoagulation (EC) for the abatement of COD, TOC, absorbance (i.e. color) and turbidity from a real textile wastewater, a pure red dye solution (disperse ...dyes 2-naphthoic acid and 2-naphthol) and a solution combining the two above fluids. The treatment of the dyestuff solution is satisfactory with high levels of color and organic pollution abatement. The treatment of the industrial waste is less efficient. Treatment of the solution combining the two above fluids allows to investigate whether the removal of several polluting matters by electrocoagulation could be considered as the superimposition of the various treatments of single-species effluents, in sort of additivity principle, as presented in an original model for the treatment of two-pollutant waste. Turbidity and TOC were shown to be additive variables in the treatment of the dye solution and the industrial textile waste: electrocoagulation seems to proceed with no interaction between the two types of matter to be removed, namely the dye stuff, and the lot of pollutants contained in the industrial waste.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectif L’AMP-activated protein kinase (AMPK) joue un rôle important dans le contrôle du métabolisme énergétique et la régulation de l’inflammation. Notre objectif est d’étudier la contribution de ...l’AMPKalpha1 du macrophage et de l’adipocyte dans l’inflammation du tissu adipeux en réponse à un régime gras. Matériels et méthodes L’insulino-résistance et l’inflammation du tissu adipeux ont été mesurées chez des souris AMPKalpha1-/- nourries avec un régime gras. Le rôle de l’AMPK du macrophage a été analysé chez des souris transplantées avec de la moelle de souris AMPKalpha1-/-. Réciproquement, l’impact de l’AMPK de l’adipocyte, a été évalué chez des souris AMPKalpha1-/- transplantées avec de la moelle AMPKalpha1+/+. Résultats Les souris AMPKalpha1-/- nourries avec un régime gras montrent une prise de poids plus importante, une augmentation de leur masse grasse et une aggravation de l’insulino-résistance et de l’inflammation du tissu adipeux. Les souris transplantées avec la moelle osseuse de souris AMPKalpha1-/- présentent une résistance à l’insuline et une inflammation accrues du tissu adipeux, mais ne développent pas d’adiposité plus grande. Par contre, les souris AMPKalpha1-/- transplantées avec la moelle AMPKalpha1+/+ ont un phénotype semblable aux souris AMPKalpha1-/-, suggérant un rôle crucial de l’AMPKalpha1 dans l’adipocyte dans la protection contre l’insulino-résistance et l’adiposité induite par régime gras. Conclusion Nos résultats montrent que l’AMPKα1 protège contre l’obésité et la résistance à l’insuline du tissu adipeux induite par régime gras et pourrait être une cible thérapeutique prometteuse dans le traitement du syndrome métabolique.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cutaneous melanoma is a deadly skin cancer that originates from melanocytes. The development of cutaneous melanoma involves a complex interaction between environmental factors, mainly ultraviolet ...radiation from sunlight, and genetic alterations. Melanoma can also occur from a pre-existing nevus, a benign lesion formed from melanocytes harboring oncogenic mutations that trigger proliferative arrest and senescence entry. Senescence is a potent barrier against tumor progression. As such, the acquisition of mutations that suppress senescence and promote cell division is mandatory for cancer development. This topic appears central to melanoma development because, in humans, several somatic and germline mutations are related to the control of cellular senescence and proliferative activity. Consequently, primary melanoma can be viewed as a paradigm of senescence evasion. In support of this notion, a sumoylation-defective germline mutation in microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte homeostasis, is associated with the development of melanoma. Interestingly, this MITF variant has also been recently reported to negatively impact the program of senescence. This article reviews the genetic alterations that have been shown to be involved in melanoma and that alter the process of senescence to favor melanoma development. Then, the transcription factor MITF and its sumoylation-defective mutant are described. How sumoylation misregulation can change MITF activity and impact the process of senescence is discussed. Finally, the contribution of such information to the development of anti-malignant melanoma strategies is evaluated.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•COD and Cr(III) species can be simultaneously removed by electrocoagulation.•Cu-containing Al alloy is more efficient than pure Al as electrodes.•Dilution of too concentrated tannery wastewater is ...required for efficient treatment.
This paper deals with the ability of electrocoagulation (EC) to remove simultaneously COD and chromium from a real chrome tanning wastewater in a batch stirred electro-coagulation cell provided with two aluminium-based electrodes (aluminium/copper/magnesium alloy and pure aluminium). Effects of operating time, current density and initial concentration of Cr(III) and COD have been investigated. The concentrations of pollutants have been successfully reduced to environmentally acceptable levels even if the concentrated effluent requires a long time of treatment of around 6h with a 400A/m2 current density. The aluminium alloy was found to be more efficient than pure aluminium for removal of COD and chromium. Dilution of the waste has been tested for treatment: high abatement levels could be obtained with shorter time of treatment and lower current densities. Energy consumption of the electrocoagulation process was also discussed. The dilution by half of the concentrated waste leads to a higher abatement performance of both COD and chromium with the best energy efficiency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed ...in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges.
Small populations (e.g., hospitals, schools or workplaces) are characterised by high contact heterogeneity and stochasticity affecting pathogen transmission dynamics. Empirical individual contact ...data provide unprecedented information to characterize such heterogeneity and are increasingly available, but are usually collected over a limited period, and can suffer from observation bias. We propose an algorithm to stochastically reconstruct realistic temporal networks from individual contact data in healthcare settings (HCS) and test this approach using real data previously collected in a long-term care facility (LTCF). Our algorithm generates full networks from recorded close-proximity interactions, using hourly inter-individual contact rates and information on individuals’ wards, the categories of staff involved in contacts, and the frequency of recurring contacts. It also provides data augmentation by reconstructing contacts for days when some individuals are present in the HCS without having contacts recorded in the empirical data. Recording bias is formalized through an observation model, to allow direct comparison between the augmented and observed networks. We validate our algorithm using data collected during the i-Bird study, and compare the empirical and reconstructed networks. The algorithm was substantially more accurate to reproduce network characteristics than random graphs. The reconstructed networks reproduced well the assortativity by ward (first–third quartiles observed: 0.54–0.64; synthetic: 0.52–0.64) and the hourly staff and patient contact patterns. Importantly, the observed temporal correlation was also well reproduced (0.39–0.50 vs 0.37–0.44), indicating that our algorithm could recreate a realistic temporal structure. The algorithm consistently recreated unobserved contacts to generate full reconstructed networks for the LTCF. To conclude, we propose an approach to generate realistic temporal contact networks and reconstruct unobserved contacts from summary statistics computed using individual-level interaction networks. This could be applied and extended to generate contact networks to other HCS using limited empirical data, to subsequently inform individual-based epidemic models.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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