Qualité physico-chimique et contamination métallique des eaux de l’Oued Hassar : impacts des eaux usées de la localité de Mediouna (Périurbain de Casablanca, Maroc)

Une des préoccupations majeures du début du XXIe siècle est la pérennité d’une ressource en eau suffisante pour satisfaire les besoins d’une  population en forte croissance dans un contexte mondial marqué par lechangement climatique et ses conséquences hydrologiques. Cette  problématique ne se limite pas à la quantité des ressources en eau, mais porte également sur leur qualité qu’il faut aujourd’hui plus que jamais bien gérer. Les activités industrielles, agricoles ou urbaines peuvent modifier la qualité des eaux et les rendre impropres à l’utilisation. C’est le cas de la zone périurbaine du Nord Est du grand Casablanca (Province de Mediouna), où le cours d’eau d’Oued Hassar reçoit, à ciel ouvert, les rejets d’eaux usées de Mediouna dont les impacts écologiques et sanitaires sont multiples. Les résultats des analyses physico-chimiques montrent que les eaux de ce cours d’eau sont caractérisées par une minéralisation  importante comme l’indiquent les valeurs élevées de la conductivité  électrique et des chlorures. De même, ces eaux présentent une pollution importante confirmée par les valeurs élevées de la DCO, le phosphore total et l’azote ammoniacal. En ce qui concerne les métaux lourds (Cd, Pb, Cr, Cu, Fe et Zn), l’analyse des résultats montre que les concentrations en éléments traces dans les eaux usées de Mediouna et de celles d’oued Hassar ne constituent pas un facteur limitant pour la réutilisation de ces eaux dans l’irrigation.Mots-clés : Casablanca, Oued Hassar, eaux usées, pollution, physicochimie, métaux lourds

Qualité bactériologique et physique des eaux de l’Oued Hassar (Casablanca, Maroc): Caractérisation et analyse en Composantes principales

The objective of this study is to evaluate the bacteriological quality of water of Oued Hassar in relation to the wastewater of Mediouna’s location and also to apply a statistical analysis using the Principal Component Analysis (PCA) to correlate data of spatio-temporal variability of bacterial indicators with those of physical parameters (temperature, pH, electrical conductivity and turbidity). The average values obtained ​​indicate that the water of this river contains a lot of amount of bacteria that indicates a faecal contamination. These values, for total coliforms, faecal coliforms and faecal Streptococci were hight and more than seven log10. Then the bacteriological quality of water of oued Hassar is classified in poor to very poor category. The Principal Component Analysis revealed that the indicator bacteria of faecal contamination presents negative correlations with the pH and the electrical conductivity, and positive correlations that are highly significant with turbidity.La présente étude consiste à évaluer la qualité bactériologique des eaux d’Oued Hassar en relation avec les effluents de la localité de Mediouna et d’appliquer une méthode statistique d’Analyse en Composantes Principales (ACP) pour corréler les données de la variabilité spatio-temporelle des indicateurs bactériologiques à ceux des paramètres physiques (température, pH, conductivité électrique et turbidité). Les valeurs moyennes obtenues révèlent que les eaux de ce cours d’eau présentent une charge très importante en bactéries indicatrices de la contamination d’origine fécale. Les teneurs en coliformes totaux, coliformes fécaux et streptocoques fécaux atteignent des valeurs importantes supérieures à sept log10. De ce fait, la qualité bactériologique des eaux d’Oued Hassar est classée dans la catégorie mauvaise à très mauvaise. L’ACP a révélé que les bactéries indicatrices de la contamination fécale présentent des corrélations négatives avec le pH et la conductivité électrique et des corrélations positives et fortement significatives avec la turbidité

Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients.

The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets

Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study.

Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088-0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/10 <sup>5</sup> CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/10 <sup>5</sup> CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively). Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. Emergex Vaccines Holding Limited

Weak Iron Oxidation by Sulfobacillus thermosulfidooxidans Maintains a Favorable Redox Potential for Chalcopyrite Bioleaching

Bioleaching is an emerging technology, describing the microbially assisted dissolution of sulfidic ores that provides a more environmentally friendly alternative to many traditional metal extraction methods, such as roasting or smelting. Industrial interest is steadily increasing and today, circa 15–20% of the world’s copper production can be traced back to this method. However, bioleaching of the world’s most abundant copper mineral chalcopyrite suffers from low dissolution rates, often attributed to passivating layers, which need to be overcome to use this technology to its full potential. To prevent these passivating layers from forming, leaching needs to occur at a low oxidation/reduction potential (ORP), but chemical redox control in bioleaching heaps is difficult and costly. As an alternative, selected weak iron-oxidizers could be employed that are incapable of scavenging exceedingly low concentrations of iron and therefore, raise the ORP just above the onset of bioleaching, but not high enough to allow for the occurrence of passivation. In this study, we report that microbial iron oxidation by Sulfobacillus thermosulfidooxidans meets these specifications. Chalcopyrite concentrate bioleaching experiments with S. thermosulfidooxidans as the sole iron oxidizer exhibited significantly lower redox potentials and higher release of copper compared to communities containing the strong iron oxidizer Leptospirillum ferriphilum. Transcriptomic response to single and co-culture of these two iron oxidizers was studied and revealed a greatly decreased number of mRNA transcripts ascribed to iron oxidation in S. thermosulfidooxidans when cultured in the presence of L. ferriphilum. This allowed for the identification of genes potentially responsible for S. thermosulfidooxidans’ weaker iron oxidation to be studied in the future, as well as underlined the need for new mechanisms to control the microbial population in bioleaching heaps

Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8(+) and CD4(+) T-cell responses with multiple specificities including a novel DR7-restricted epitope.

Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-179-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8(+) and CD4(+) T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-189-102 for CD8(+) and NY-ESO-183-99 for CD4(+) T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187-99); 7/7 HLA-DR7(+) patients generated strong CD4(+) T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-179-108 peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8(+) and CD4(+) T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma.

Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8 <sup>+</sup> T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO). Interestingly, similar associations were seen in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive mechanisms. Lymph vessel associated T cell infiltration may increase immunotherapy success rates provided that the treatment overcomes adaptive immune resistance

Entourage: the immune microenvironment following follicular lymphoma

In follicular lymphoma, nonmalignant immune cells are important. Follicular lymphoma depends on CD4+ cells, but CD8+ cells counteract it. We hypothesized that the presence of follicular lymphoma is associated with higher CD4+ than CD8+ cell numbers in the tumor microenvironment but not in the immune system. Using flow cytometry, pre-treatment and follow-up CD4/CD8 ratios were estimated in the bone marrow, blood and lymph nodes of untreated follicular lymphoma patients in two independent data sets (N1=121; N2=166). The ratios were analyzed for their relation with bone marrow lymphoma involvement. Bone marrows were also investigated with immunohistochemistry. In either data set, the bone marrow CD4/CD8 ratios were higher in bone marrows involved with lymphoma (P=0.043 and 0.0002, respectively). The mean CD4/CD8 ratio was 1.0 in uninvolved and 1.4 in involved bone marrows. Also higher in involved bone marrows were CD4/CD56 and CD3CD25/CD3 ratios. No blood or lymph node ratios differed between bone marrow-negative and -positive patients. Sequential samples showed increased bone marrow CD4/CD8 ratios in all cases of progression to bone marrow involvement. Immunohistochemistry showed CD4+, CD57+, programmed death-1+, forkhead box protein 3+ and CD21+ cells accumulated inside the lymphoma infiltrates, whereas CD8+, CD56+ and CD68+ cells were outside the infiltrates. This study provides evidence in vivo that the microenvironment changes upon follicular lymphoma involvement