Hydrocarbons in size-fractionated plankton of the Mediterranean Sea (MERITE-HIPPOCAMPE campaign).

Aliphatic and polycyclic aromatic hydrocarbons (AHs and PAHs, respectively) were analyzed in the dissolved fraction (<0.7 µm) of surface water and in various particulate/planktonic size fractions (0.7-60, 60-200, 200-500 and 500-1000 µm) collected at the deep chlorophyll maximum, along a North-South transect in the Mediterranean Sea in spring 2019 (MERITE-HIPPOCAMPE campaign). Suspended particulate matter, biomass, total chlorophyll a, particulate organic carbon, C and N isotopic ratios, and lipid biomarkers were also determined to help characterizing the size-fractionated plankton and highlight the potential link with the content in AHs and PAHs in these size fractions. Æ©28AH concentrations ranged 18-489 ng L-1 for water, 3.9-72 µg g-1 dry weight (dw) for the size fraction 0.7-60 µm, and 3.4-55 µg g-1 dw for the fractions 60-200, 200-500 and 500-1000 µm. AH molecular profiles revealed that they were mainly of biogenic origin. Æ©14PAH concentrations were 0.9-16 ng L-1 for water, and Æ©27PAH concentrations were 53-220 ng g-1 dw for the fraction 0.7-60 µm and 35-255 ng g-1 dw for the three higher fractions, phenanthrene being the most abundant compound in planktonic compartment. Two processes were evidenced concerning the PAH patterns, the bioreduction, i.e., the decrease in concentrations from the small size fractions (0.7-60 and 60-200 µm) to the higher ones (200-500 µm and 500-1000 µm), and the biodilution, i.e., the decrease in concentrations in plankton at higher suspended matter or biomass, especially for the 0.7-60 and 60-200-µm size fractions. We estimated the biological pump fluxes of Æ©27PAHs below 100-m depth in the Western Mediterranean Sea at 15 ± 10 ng m-2 day-1, which is comparable to those previously reported in the South Pacific and Indian Ocean.

ß-Cell Stress Shapes CTL Immune Recognition of Preproinsulin Signal Peptide by Posttranscriptional Regulation of Endoplasmic Reticulum Aminopeptidase 1.

The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)-mediated ß-cell destruction in type 1 diabetes (T1D). Among them, the 10-mer epitope located at the C-terminal end of the signal peptide was found to be the most prevalent in patients with recent-onset T1D. While the combined action of signal peptide peptidase and endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) is required for processing of the signal peptide, the mechanisms controlling signal peptide trimming and the contribution of the T1D inflammatory milieu on these mechanisms are unknown. Here, we show in human ß-cells that ER stress regulates ERAP1 gene expression at posttranscriptional level via the IRE1α/miR-17-5p axis and demonstrate that inhibition of the IRE1α activity impairs processing of preproinsulin signal peptide antigen and its recognition by specific autoreactive CTLs during inflammation. These results underscore the impact of ER stress in the increased visibility of ß-cells to the immune system and position the IRE1α/miR-17 pathway as a central component in ß-cell destruction processes and as a potential target for the treatment of autoimmune T1D.

Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome.

OBJECTIVE: Atypical manifestations have been described in patients with ANCA-associated vasculitides (AAV), such as pachymeningitis, orbital mass or chronic periaortitis. Because these manifestations have been associated to the spectrum of IgG4-related disease (IgG4-RD), we hypothesized that both diseases could overlap. METHODS: We conducted a European retrospective multicenter observational study including patients fulfilling ACR and Chapel Hill criteria for AAV and IgG4-RD Comprehensive Diagnostic Criteria. RESULTS: Eighteen patients were included (median age 55.5years, 13 men). AAV and IgG4-RD were diagnosed concomitantly in 13/18 (72%) patients; AAV preceded IgG4-RD in 3/18 (17%) while IgG4-RD preceded AAV in 2/18 (11%). AAV diagnoses included granulomatosis with polyangiitis in 14 (78%), microscopic polyangiitis in 3 (17%), and eosinophilic granulomatosis with polyangiitis in one case. IgG4-RD diagnosis included definite IgG4-RD in 5 (28%) cases, probable IgG4-RD in 5 (28%) and possible IgG4-RD in 8 (44%). IgG4-RD manifestations were chronic periaortitis in 9/18 (50%) patients, orbital mass and tubulointerstitial nephritis in 4 (22%) cases, prevertebral fibrosis in 3 (17%), pachymeningitis and autoimmune pancreatitis in 2 (11%) cases. Patients required median number of 2 (range 0-4) lines of immunosuppressants in combination with glucocorticoids. During the follow-up (median 49,8months, range 17,25-108months), AAV manifestations relapsed in 10/18 (56%) cases and IgG4-RD lesions in 5/18 (28%). When used, mainly for relapses, rituximab showed response in all cases. CONCLUSION: AAV and IgG4-RD may overlap. Clinicians should consider that atypical manifestations during AAV could be related to IgG4-RD rather than to refractory granulomatous or vasculitic lesions.

Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions.

BACKGROUND: Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS). OBJECTIVES: We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers. METHODS: Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples. RESULTS: Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P < 0·001), and in nodular vs. macular/papular KS lesions (P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors. CONCLUSIONS: The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.

Optimizing reporter constructs for in vivo bioluminescence imaging of interferon-γ stimulated mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) are a promising treatment modality for a variety of diseases. Strategies to investigate the fate of MSCs in vivo are important to unravel their therapeutic mechanisms. However, currently available techniques are hampered by their low sensitivity. We therefore aimed to optimize in vivo bioluminescence imaging of MSCs. We compared MSCs transduced with firefly luciferase (Fluc) and transmembrane-bound Gaussia luciferase driven by the human cytomegalovirus, spleen focus-forming virus (SFFV), and elongation factor 1-α (EF1α) promoters. Although cytomegalovirus-transmembrane-bound Gaussia luciferase-transduced MSCs showed the highest light intensity in vitro, the signal was almost undetectable in vivo. Spleen focus-forming virus-Fluc-transduced MSCs revealed a bright signal in vivo, but transgene expression was silenced upon in vitro stimulation with interferon (IFN)-γ. Therefore, the SFFV promoter was replaced by the EF1α promoter. Light emission of Fluc under the control of EF1α was similar to SFFV-Fluc. Although EF1α-Fluc light emission was decreased tenfold in the presence of IFN-γ when compared with unstimulated MSCs, the bioluminescent signal could still be detected and was clearly distinguishable from untransduced MSCs. Furthermore, stimulation of MSCs with tumor necrosis factor-α hardly affected transgene expression in EF1α-Fluc-transduced MSCs. Thus, the use of the EF1α promoter partially overcomes silencing and allows in vivo bioluminescence imaging of IFN-γ-stimulated MSCs.

FcgammaRIIIA and FcgammaRIIA polymorphisms do not predict clinical outcome of follicular non-Hodgkin's lymphoma patients treated with sequential CHOP and rituximab.

We analyzed FcgammaRIIIA-158V/F and FcgammaRIIA-131H/R polymorphisms in a cohort of 94 newly diagnosed follicular lymphoma (FL) patients sequentially treated with CHOP and Rituximab. With a median follow-up of 5.8 years, the overall survival at 8 years is 83%. Univariate and multivariate analysis showed no correlation between FcgammaRIIIA-158VV/VF and FcgammaRIIA-131HH/HR polymorphisms and the overall response rate, the molecular response and the event-free survival obtained after CHOP and Rituximab. By contrast, the achievement of a durable molecular clearance of BCL2/IgH+ cells detectable in the bone marrow is confirmed to be a reliable predictive factor of a better long-term clinical outcome.

Nocardia pseudobrasiliensis sp. nov., a new species of Nocardia which groups bacterial strains previously identified as Nocardia brasiliensis and associated with invasive diseases.

We studied five strains of a new Nocardia taxon recently identified among Nocardia brasiliensis strains associated with invasive diseases (R. J. Wallace, Jr., B. A. Brown, Z. Blacklock, R. Ulrich, K. Jost, J. M. Brown, M. M. McNeil, G. Onyi, V. A. Steingrube, and J. Gibson, J. Clin. Microbiol. 33:1528-1533, 1995) to determine their taxonomic status. Several characteristics of these organisms, including the presence of chemotype IV cell walls, nocardomycolic acids, a predominant menaquinone similar to that of Nocardia asteroides ATCC 19247T (T = type strain), and G+C contents ranging from 67 to 68 mol%, are characteristics of the genus Nocardia. Phylogenies based on small-subunit ribosomal DNA sequences clearly confirmed that all five strains belong to the genus Nocardia and occur on a single branch that is clearly distinct from N. brasiliensis. This branch forms a clade with Nocardia vaccinii, Nocardia nova, Nocardia otitidiscaviarum, and Nocardia seriolae. The five new strains exhibited high levels of DNA relatedness with each other, as determined by DNA-DNA hybridization experiments (S1 nuclease procedure), but not with N. brasiliensis strains or with strains of the four phylogenetically related Nocardia species mentioned above. The five new strains differ from N. brasiliensis in the following characteristics: mycolic acid pattern, decomposition of adenine, nitrate reduction, and antimicrobial agent susceptibilities. Therefore, we propose that these strains belong to a new species, Nocardia pseudobrasiliensis. The type strain is strain ATCC 51512, which was isolated from a leg abscess on a patient suffering from ulcerative colitis.

Turicella otitidis gen. nov., sp. nov., a coryneform bacterium isolated from patients with otitis media.

The partial 16S rRNA gene sequences of some coryneform bacteria isolated from middle-ear fluids from patients with otitis media were determined. A comparative analysis performed with rRNA sequences of other high-G + C-content gram-positive bacteria showed that the coryneform bacteria isolated from otitis media patients were only remotely related to members of previously described genera. On the basis of the results of the phylogenetic analysis and previously published biochemical and chemotaxonomic data, we propose that the strains isolated from middle-ear infections should be classified in a new genus, Turicella, as Turicella otitidis gen. nov., sp. nov. The type strain of T. otitidis is strain DSM 8821.

Chemotaxonomy and molecular taxonomy of some coryneform clinical isolates.

Six reference strains of the genus Brevibacterium as well as fifteen clinical isolates tentatively assigned to the genus using conventional biochemical methods, were the subject of chemotaxonomic and DNA similarity studies. Five of these clinical isolates were assigned either to the genera Aureobacterium, Mycobacterium, Gordona or to Rhodococcus on the basis of their DNA mol% G+C, mycolic acid, amino-acid, sugar and menaquinone contents. Among the ten remaining strains, six were not brevibacteria and only four conformed to the description of the genus Brevibacterium sensu stricto. These strains showed low values of DNA relatedness with Brevibacterium epidermidis ATCC 35514T and Brevibacterium linens ATCC 9174, and could only be described as Brevibacterium spp. The results indicate that studies of chemical markers are essential for the correct identification of brevibacteria.