Electronic Waste Recycling and Disposal: An Overview

Electronic waste, or e-waste, is said to be the fastest growing stream of hazardous waste in the world. E-waste is comprised of a variety of inputs including hazardous materials, potentially valuable and recyclable materials, and other inputs. E-waste follows a range of pathways after disposal, including formal and informal recycling, storage, and dumping, in both developed and less-developed country contexts. Globally, the handling and regulation of e-waste as both a hazardous waste stream and as a source of secondary raw materials has undergone significant changes in the past decade. A growing number of countries have adopted extended producer responsibility laws, which mandate electronics manufacturers to pay for proper recycling and disposal of electronics. The e-waste recycling industry is becoming more formalized as the potential to recover valuable materials has increased, but a range of recent studies have shown that e-waste recycling continues to carry a range of occupational health and environmental risks

La surexpression de p21 WAF1/CIP1 via CUGP1 et les Granules de Stress procurent une résistance aux cellules cancéreuses face à l'apoptose médiée par le Bortézomib

Raisonnement: Les mécanismes post-transcriptionnels occupent une place importante au sein de la régulation de l’expression génique. L’expression génique est cruciale au bon développement de la cellule, mais également à sa survie. L’altération des mécanismes post-transcriptionnels fait maintenant l'objet de nombreuses études sur la cause ou la conséquence de différentes pathologies humaines telles que le cancer. Récemment, les Granules de Stress (GS) ont été trouvées à agir comme un nouveau mécanisme post-transcriptionnel, qui permet à la cellule de survivre en conditions de stress. Résultats: Notre étude démontre pour la première fois, la formation de GS dans les cellules cancéreuses traitées avec un agent chimiothérapeutique. De cela, nous avons élucidé un sentier spécifique de formation des GS en réponse au Bortézomib (Bz). Nous avons montré que cet inhibiteur de protéasome réduit l’initiation de la traduction via la phosphorylation du facteur de l’initiation de la traduction (eIF2). Cette phosphorylation d’eIF2 se produit via l’activation de la kinase de stress HRI (Heme-Regulated kinase). La suppression de la voie de phosphorylation d’eIF2-GS via la déplétion de HRI favorise une mort cellulaire accrue chez les cellules cancéreuses traitées au Bz. Ces données révèlent donc un rôle important pour HRI dans la résistance des cellules cancéreuses face au Bz, en partie par l’entremise de sa capacité à réguler la formation de GS. Pour faire suite à cette étude, nous décrivons que le facteur anti-apoptotique p21 est séquestré à l’intérieur des GS qui sont induites par le Bz. L’emprisonnement de l’ARNm p21, hautement instable, à l’intérieur des GS permet à cet ARNm d’être protégé, stabilisé et donc accumulé. Nous démontrons que la protéine de liaison à l’ARN, CUGBP1, est responsable de la localisation de l’ARNm p21 à l’intérieur des GS en réponse au Bz. Après un traitement prolongé de Bz, les GS sont désassemblées et ainsi relâchent une grande quantité d’ARNm p21 qui devient alors disponible pour être traduite. Cette traduction massive de p21 apporte alors un élan anti-apoptotique à la cellule cancéreuse ce qui lui permet de survivre au traitement chimiothérapeutique de Bz. Conclusions et perspectives: En somme, ces études décrivent une nouvelle voie spécifique de survie cellulaire qui implique un rôle potentiel pour les GS dans le cancer et qui pourrait être ciblée en thérapie. En perspective, des tumeurs xénogreffes chez la souris seront utilisées pour tester si (i) la suppression des GS via l’inactivation de HRI, et (ii) l’inactivation de la voie CUGBP1-p21, qui est régulée par les GS, sensibiliseraient les tumeurs au Bz, validant ainsi notre modèle in vivo. Ces études apporteraient des preuves de concept pour le développement de nouvelles stratégies ciblant les voies associées au GS et qui pourraient être utilisées en thérapie combinatoire pour diminuer le risque de résistance face au traitement de Bz.Rationale: Post-transcriptional mechanisms play an important role in the regulation of gene expression. Gene expression is crucial for the proper development of the cell but also for its survival. The alteration of post-transcriptional mechanisms is now the subject of numerous studies on the cause, or on the consequence, of various human diseases such as cancer. Recently, Stress Granules (SG) have been found to act as a new post-transcriptional mechanism, which allows the cell to survive in stress conditions. Results: Our study demonstrates for the first time, the formation of SGs in cancerous cells, in response to a chemotherapeutic agent. From this we have elucidated a specific pathway of SG formation in response to Bortezomib (Bz). We demonstrate herein that this proteasome inhibitor reduces translation initiation via the phosphorylation of the initiation factor (eIF2). This phosphorylation of eIF2 is controlled through the activation of the heme-regulated kinase (HRI). The alteration of the pathway phospho-eIf2-SG, through depletion of HRI, causes massive cellular death in Bz treated cancerous cells. These data thus reveal a crucial role for HRI in the resistance of cancerous cells against Bz, in part via its capacity to regulate SG formation. Furthermore, we describe the anti-apoptotic factor p21 to be trapped inside Bz-SGs. This sheltering of the highly unstable p21 mRNA allows this one to be protected from degradation, which can be stabilized and accumulated. We also demonstrate, herein, that the RNA-binding protein CUGBP1 acts as a factor responsible for the localization of the p21 mRNA inside Bz-SGs. After prolonged treatment of Bz, SGs disassemble and release a high dose of p21 mRNA that becomes available for translation. This massive translation of anti-apoptotic p21 gives a boost to the cell that allows it to survive the stress. Perspectives and Conclusion: In sum, our studies describe a new specific pathway of cell survival that implies a potential role for SGs in cancer, which could be targeted in therapy. In perspective, xenograft tumors in mice will be used to test if (i) the inhibition of SG formation via the inactivation of HRI, and (ii) the inactivation of the CUGBP1-p21 pathway that is regulated by SGs, can both sensitize tumors to Bz treatment thus validating our model in vivo. These studies will provide us with a proof of principle for the development of new strategies targeting SG-associated pathways. Combinatorial therapies implicating the termination of such pathways could be developped in order to reduce the risk of recurrence against Bz

The chemotherapeutic agent bortezomib induces the formation of stress granules

BACKGROUND: Cytoplasmic stress granules (SGs) are specialized storage sites of untranslated mRNAs whose formation occurs under different stress conditions and is often associated with cell survival. SGs-inducing stresses include radiations, hypoxia, viral infections, and chemical inhibitors of specific translation initiation factors. The FDA-approved drug bortezomib (Velcade(®)) is a peptide boronate inhibitor of the 26S proteasome that is very efficient for the treatment of myelomas and other hematological tumors. Solid tumors are largely refractory to bortezomib. In the present study, we investigated the formation of SGs following bortezomib treatment. RESULTS: We show that bortezomib efficiently induces the formation of SGs in cancer cells. This process involves the phosphorylation of translation initiation factor eIF2α by heme-regulated inhibitor kinase (HRI). Depletion of HRI prevents bortezomib-induced formation of SGs and promotes apoptosis. CONCLUSIONS: This is the first study describing the formation of SGs by a chemotherapeutic compound. We speculate that the activation of HRI and the formation of SGs might constitute a mechanism by which cancer cells resist bortezomib-mediated apoptosis

From Waste to Resources? Interrogating ‘Race to the Bottom’ in the Global Environmental Governance of the Hazardous Waste Trade

The rise of global environmental governance regimes allegedly contradicts the process of an environmental “race to the bottom” (RTB) that results from capitalist globalization. We examine new developments in this area through a qualitative case study of the Basel Convention. Here, we find that new regulations in toxic wastes governance are in fact being co-created with industry actors and aim to accelerate the flow of toxic “resources” to less-developed countries. Further, these shifts are legitimized by a shift in discourse— from thinking of toxics materials as “wastes” to thinking of them as “resources”— that re-frames the toxic wastes trade as essential for sustainable economic development rather than as a manifestation of global environmental injustice, thereby undermining environmentalist claims. Our findings suggest that, despite an expansion of hazardous waste regulations, the RTB concept is still relevant in the context of global environmental governance. We conclude that a fruitful avenue for applying the RTB concept in this context is to go beyond a strict materialist interpretation of global politics to also consider the role of discourses and contesting ideologies in shaping global environmental policy debates.</em

Machine Learning in Melanoma Diagnosis. Limitations About to be Overcome

[spa] Antecedentes: La clasificación automática de imágenes es una rama prometedora del aprendi-zaje automático (de sus siglas en inglés Machine Learning [ML]), y es una herramienta útil enel diagnóstico de cáncer de piel. Sin embargo, poco se ha estudiado acerca de las limitacionesde su uso en la práctica clínica diaria.Objetivo: Determinar las limitaciones que existen en cuanto a la selección de imágenes usadaspara el análisis por ML de las neoplasias cutáneas, en particular del melanoma.Métodos: Se dise ̃nó un estudio de cohorte retrospectivo, donde se incluyeron de forma conse-cutiva 2.849 imágenes dermatoscópicas de alta calidad de tumores cutáneos para su valoraciónpor un sistema de ML, recogidas entre los a ̃nos 2010 y 2014. Cada imagen dermatoscópica fueclasificada según las características de elegibilidad para el análisis por ML.Resultados: De las 2.849 imágenes elegidas a partir de nuestra base de datos, 968 (34%) cum-plieron los criterios de inclusión. De los 528 melanomas, 335 (63,4%) fueron excluidos. Laausencia de piel normal circundante (40,5% de todos los melanomas de nuestra base de datos)y la ausencia de pigmentación (14,2%) fueron las causas más frecuentes de exclusión para elanálisis por ML.Discusión: Solo el 36,6% de nuestros melanomas se consideraron aceptables para el análisispor sistemas de ML de última generación. Concluimos que los futuros sistemas de ML deberánser entrenados a partir de bases de datos más grandes que incluyan imágenes representativasde la práctica clínica habitual. Afortunadamente, muchas de estas limitaciones están siendosuperadas gracias a los avances realizados recientemente por la comunidad científica, como seha demostrado en trabajos recientes. [eng] Background: Automated image classification is a promising branch of machine learning (ML)useful for skin cancer diagnosis, but little has been determined about its limitations for generalusability in current clinical practice.Objective: To determine limitations in the selection of skin cancer images for ML analysis,particularly in melanoma.Methods: Retrospective cohort study design, including 2,849 consecutive high-quality dermos-copy images of skin tumors from 2010 to 2014, for evaluation by a ML system. Each dermoscopyimage was assorted according to its eligibility for ML analysis.Results: Of the 2,849 images chosen from our database, 968 (34%) met the inclusion criteriafor analysis by the ML system. Only 64.7% of nevi and 36.6% of melanoma met the inclusioncriteria. Of the 528 melanomas, 335 (63.4%) were excluded. An absence of normal surroundingskin (40.5% of all melanomas from our database) and absence of pigmentation (14.2%) were themost common reasons for exclusion from ML analysis.Discussion: Only 36.6% of our melanomas were admissible for analysis by state-of-the-art MLsystems. We conclude that future ML systems should be trained on larger datasets which includerelevant non-ideal images from lesions evaluated in real clinical practice. Fortunately, many ofthese limitations are being overcome by the scientific community as recent works show

p21WAF1/CIP1 Upregulation through the Stress Granule-Associated Protein CUGBP1 Confers Resistance to Bortezomib-Mediated Apoptosis

p21(WAF1/CIP1) is a well known cyclin-dependent kinase inhibitor induced by various stress stimuli. Depending on the stress applied, p21 upregulation can either promote apoptosis or prevent against apoptotic injury. The stress-mediated induction of p21 involves not only its transcriptional activation but also its posttranscriptional regulation, mainly through stabilization of p21 mRNA levels. We have previously reported that the proteasome inhibitor MG132 induces the stabilization of p21 mRNA, which correlates with the formation of cytoplasmic RNA stress granules. The mechanism underlying p21 mRNA stabilization, however, remains unknown.We identified the stress granules component CUGBP1 as a factor required for p21 mRNA stabilization following treatment with bortezomib ( =  PS-341/Velcade). This peptide boronate inhibitor of the 26S proteasome is very efficient for the treatment of myelomas and other hematological tumors. However, solid tumors are sometimes refractory to bortezomib treatment. We found that depleting CUGBP1 in cancer cells prevents bortezomib-mediated p21 upregulation. FISH experiments combined to mRNA stability assays show that this effect is largely due to a mistargeting of p21 mRNA in stress granules leading to its degradation. Altering the expression of p21 itself, either by depleting CUGBP1 or p21, promotes bortezomib-mediated apoptosis.We propose that one key mechanism by which apoptosis is inhibited upon treatment with chemotherapeutic drugs might involve upregulation of the p21 protein through CUGBP1

From Waste to Resources?: Interrogating \u27Race to the Bottom\u27 in the Global Environmental Governance of the Hazardous Waste Trade

<em>The rise of global environmental governance regimes allegedly contradicts the process of an environmental “race to the bottom” (RTB) that results from capitalist globalization. We examine new developments in this area through a qualitative case study of the Basel Convention. Here, we find that new regulations in toxic wastes governance are in fact being co-created with industry actors and aim to </em>accelerate<em> the flow of toxic “resources” to less-developed countries. Further, these shifts are legitimized by a shift in discourse— from thinking of toxics materials as “wastes” to thinking of them as “resources”— that re-frames the toxic wastes trade as essential for sustainable economic development rather than as a manifestation of global environmental injustice, thereby undermining environmentalist claims. Our findings suggest that, despite an expansion of hazardous waste regulations, the RTB concept is still relevant in the context of global environmental governance. We conclude that a fruitful avenue for applying the RTB concept in this context is to go beyond a strict materialist interpretation of global politics to also consider the role of discourses and contesting ideologies in shaping global environmental policy debates.</em

The chemotherapeutic agent bortezomib induces the formation of stress granules

Abstract Background Cytoplasmic stress granules (SGs) are specialized storage sites of untranslated mRNAs whose formation occurs under different stress conditions and is often associated with cell survival. SGs-inducing stresses include radiations, hypoxia, viral infections, and chemical inhibitors of specific translation initiation factors. The FDA-approved drug bortezomib (Velcade®) is a peptide boronate inhibitor of the 26S proteasome that is very efficient for the treatment of myelomas and other hematological tumors. Solid tumors are largely refractory to bortezomib. In the present study, we investigated the formation of SGs following bortezomib treatment. Results We show that bortezomib efficiently induces the formation of SGs in cancer cells. This process involves the phosphorylation of translation initiation factor eIF2α by heme-regulated inhibitor kinase (HRI). Depletion of HRI prevents bortezomib-induced formation of SGs and promotes apoptosis. Conclusions This is the first study describing the formation of SGs by a chemotherapeutic compound. We speculate that the activation of HRI and the formation of SGs might constitute a mechanism by which cancer cells resist bortezomib-mediated apoptosis.</p

Characterization of Fragile X Mental Retardation Protein granules formation and dynamics in Drosophila

Summary FMRP is an evolutionarily conserved protein that is highly expressed in neurons and its deficiency causes fragile X mental retardation syndrome. FMRP controls the translation of target mRNAs in part by promoting their dynamic transport in neuronal RNA granules. We have previously shown that high expression of mammalian FMRP induces formation of granules termed FMRP granules. These RNA granules are reminiscent of neuronal granules, of stress granules, as well as of the recently described in vitro-assembled granules. In contrast with mammalian FMRP, which has two paralog proteins, Drosophila FMRP (dFMRP) is encoded by a single gene that has no paralog. Using this genetically simple organism, we investigated formation and dynamics of FMRP granules. We found that increased expression of dFMRP in Drosophila cells induces the formation of dynamic dFMRP RNA granules. Mutagenesis studies identified the N-terminal protein–protein domain of dFMRP as a key determinant for FMRP granules formation. The RGG RNA binding motif of dFMRP is dispensable for dFMRP granules formation since its deletion does not prevent formation of those granules. Deletion of the RGG motif reduced, however, dFMRP trafficking between FMRP granules and the cytosol. Similarly, deletion of a large part of the KH RNA binding motif of dFMRP had no effect on formation of dFMRP-granules, but diminished the shuttling activity of dFMRP. Our results thus suggest that the mechanisms controlling formation of RNA granules and those promoting their dynamics are uncoupled. This study opens new avenues to further elucidate the molecular mechanisms controlling FMRP trafficking with its associated mRNAs in and out of RNA granules