Decrease in the photosynthetic performance of temperate grassland species does not lead to a decline in the gross primary production of the ecosystem

Plants, under stressful conditions, can proceed to photosynthetic adjustments in order to acclimatize and alleviate the detrimental impacts on the photosynthetic apparatus. However, it is currently unclear how adjustment of photosynthetic processes under environmental constraints by plants influences CO2 gas exchange at the ecosystem-scale. Over a two-year period, photosynthetic performance of a temperate grassland ecosystem was characterized by conducting frequent chlorophyll fluorescence (ChlF) measurements on three primary grassland species (Lolium perenne L., Taraxacum sp., and Trifolium repens L.). Ecosystem photosynthetic performance was estimated from measurements performed on the three dominant grassland species weighed based on their relative abundance. In addition, monitoring CO2 fluxes was performed by eddy covariance. The highest decrease in photosynthetic performance was detected in summer, when environmental constraints were combined. Dicot species (Taraxacum sp. and T. repens) presented the strongest capacity to up-regulate PSI and exhibited the highest electron transport efficiency under stressful environmental conditions compared with L. perenne. The decline in ecosystem photosynthetic performance did not lead to a reduction in gross primary productivity, likely because increased light energy was available under these conditions. The carbon amounts fixed at light saturation were not influenced by alterations in photosynthetic processes, suggesting photosynthesis was not impaired. Decreased photosynthetic performance was associated with high respiration flux, but both were influenced by temperature. Our study revealed variation in photosynthetic performance of a grassland ecosystem responded to environmental constraints, but alterations in photosynthetic processes appeared to exhibit a negligible influence on ecosystem CO2 fluxes

The interplay of extracellular matrix and microbiome in urothelial bladder cancer

Many pathological changes in solid tumours are caused by the accumulation of genetic mutations and epigenetic molecular alterations. In addition, tumour progression is profoundly influenced by the environment surrounding the transformed cells. The interplay between tumour cells and their microenvironment has been recognized as one of the key determinants of cancer development and is being extensively investigated. Data suggest that both the extracellular matrix and the microbiota represent microenvironments that contribute to the onset and progression of tumours. Through the introduction of omics technologies and pyrosequencing analyses, a detailed investigation of these two microenvironments is now possible. In urological research, assessment of their dysregulation has become increasingly important to provide diagnostic, prognostic and predictive biomarkers for urothelial bladder cancer. Understanding the roles of the extracellular matrix and microbiota, two key components of the urothelial mucosa, in the sequelae of pathogenic events that occur in the development and progression of urothelial carcinomas will be important to overcome the shortcomings in current bladder cancer treatment strategies

L’année 2021 dans tous ses états : une synthèse digérée

International audience5548 Background: Ovarian cancer is the leading cause of death by gynecological cancer. Complete surgery remains one of the main prognostic factors. Laparoscopic exploration is mandatory to assess surgical resectability at diagnosis or after neoadjuvant chemotherapy. However, there is no clinical or biological marker that can correctly predict resectability and may be able to avoid a second laparoscopic exploration for initially unresectable diseases. Our aim was to assess circulating tumor DNA (ctDNA) value as a predictive non-invasive marker of evolution towards resectability for patients with epithelial ovarian cancer receiving first-line chemotherapy. Methods: We explored in this work one of the secondary objectives of the CIDOC study (NCT03302884). CIDOC is a multicenter prospective study aiming to explore ctDNA value as early marker of disease relapse after first-line treatment for epithelial ovarian cancer. Patients with mucinous histology or early stages not requiring chemotherapy are excluded. Plasma samples are collected at diagnosis, during neoadjuvant chemotherapy, and during follow-up. After DNA extraction, panel-based next generation sequencing is performed on both tumor samples and germline DNA, and somatic mutations of interest are selected for ctDNA monitoring. ctDNA analyses are conducted using droplet digital PCR (BioRad QX200) by measuring the variant allele fraction (VAF) of previously identified mutations. Results: This intermediary analysis has included 47 patients diagnosed between March 2017 and December 2019. Median age was 69 years old (48 – 84). Most of the patients had advanced disease (89.4% stage FIGO III or IV), serous histology (94.8%), and high grade tumor (92.3%). Most of the patients underwent complete interval cytoreductive surgery (76.3% vs 17.4% complete upfront surgery). Most of the tumors had TP53 mutations (85.1%), following by alterations involving DNA repair genes (38.3%). Median cell-free DNA concentration at baseline was 0.38 ng/µL (0 – 12.8). ctDNA was identified in 92.1% of patients at baseline with a median VAF of 1.84% (0 – 42.52%). ctDNA VAF was correlated to the peritoneal dissemination ( p= 0.039) assessed with the peritoneal cancer index. ctDNA clearance after preoperative chemotherapy tended to be correlated to achievement of complete interval surgery for patients receiving neoadjuvant chemotherapy ( p= 0.108). Conclusions: ctDNA may be a promising non-invasive marker to assess peritoneal cancer spreading and to predict surgical resectability after neoadjuvant chemotherapy. If confirmed in larger populations, this may enable to avoid additional surgical explorations for patients who remain ctDNA positive after chemotherapy. Clinical trial information: NCT03302884

Doravirine plus lamivudine two-drug regimen as maintenance antiretroviral therapy in people living with HIV: a French observational study

International audienceBackground: Two-drug regimens based on integrase strand transfer inhibitors (INSTIs) and boosted PIs have entered recommended ART. However, INSTIs and boosted PIs may not be suitable for all patients. We aimed to report our experience with doravirine/lamivudine as maintenance therapy in people living with HIV (PLWH) followed in French HIV settings.Methods: This observational study enrolled all adults who initiated doravirine/lamivudine between 1 September 2019 and 31 October 2021, in French HIV centres participating in the Dat'AIDS cohort. The primary outcome was the rate of virological success (plasma HIV-RNA < 50 copies/mL) at Week (W)48. Secondary outcomes included: rate of treatment discontinuation for non-virological reasons, evolution of CD4 count and CD4/CD8 ratio over follow-up.Results: Fifty patients were included, with 34 (68%) men; median age: 58 years (IQR 51-62), ART duration: 20 years (13-23), duration of virological suppression: 14 years (8-19), CD4 count: 784 cells/mm3 (636-889). Prior to switching, all had plasma HIV-RNA < 50 copies/mL. All but three were naive to doravirine, and 36 (72%) came from a three-drug regimen. Median follow-up was 79 weeks (IQR 60-96). Virological success rate at W48 was 98.0% (95% CI 89.4-99.9). One virological failure occurred at W18 (HIV-RNA = 101 copies/mL) in a patient who briefly discontinued doravirine/lamivudine due to intense nightmares; there was no resistance at baseline and no resistance emergence. There were three strategy discontinuations for adverse events (digestive disorders: n = 2; insomnia: n = 1). There was no significant change in CD4/CD8 ratio, while CD4 T cell count significantly increased.Conclusions: These preliminary findings suggest that doravirine/lamivudine regimens can maintain high levels of viral suppression in highly ART-experienced PLWH with long-term viral suppression, and good CD4+ T cell count