Centre INRAE Grand-Est - Colmar

Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P<0.0001 and P=0.001, respectively). Considering long-term toxicity, the addition of rituximab in the first-line setting was confirmed as safe with regards to development of secondary malignancies. Long-term follow up of patients with follicular lymphoma treated in the FL2000 study confirms the sustained clinical benefit of rituximab without long-term toxicity.

BACKGROUND: Longitudinal studies of dementia with Lewy bodies (DLB) are rare. Clinically, DLB is usually considered to worsen into Alzheimer's disease (AD). The aim of our study was to compare the rate of the cognitive decline in DLB, AD, and the association of the two diseases (AD + DLB). METHODS: Using the Regional Network for Diagnostic Aid and Management of Patients with Cognitive Impairment database, which includes all the patients seen at all memory clinics (medical consultation and day hospitals) in four French regions, and beta regression, we compared the longitudinal the Mini-Mental State Examination scores of 1159 patients with AD (n = 1000), DLB (n = 131) and AD + DLB (association of the two) (n = 28) during follow-up of at least 4 years. RESULTS: The mean follow-up of the patients was 5.88 years. Using beta regression without propensity scores, the comparison of the decline of patients with AD and patients with DLB did not show a significant difference, but the decline of patients with AD + DLB was worse than that of either patients with DLB (P = 0.006) or patients with AD (P < 0.001). Using beta regression weighted by a propensity score, comparison of patients with AD and patients with DLB showed a faster decline for patients with DLB (P < 0.001). The comparison of the decline of patients with AD + DLB with that of patients with DLB (P < 0.001) and patients with AD (P < 0.001) showed that the decline was clearly worse in the patients with dual disease. CONCLUSIONS: Whatever the analysis, the rate of decline is faster in patients with AD + DLB dual disease. The identification of such patients is important to enable clinicians to optimise treatment and care and to better inform and help patients and caregivers.

SUMMARY: To evaluate the reliability of the arthroscopic assessment of full-thickness rotator cuff tears, 117 cases were prospectively investigated by imaging, arthroscopy, and open surgery. The confidence of the surgeon, his accuracy, and the surgeon-dependent character of arthroscopic assessment were evaluated in terms of the description of the main anatomic parameters. The surgeons were confident and accurate in diagnosing a full-thickness tear of the supraspinatus, but they underestimated its coronal and sagittal extent and its reducibility to the greater tuberosity. Conversely, the technique appeared very accurate in describing the rotator interval. Endoscopic assessment was particularly operator-dependent in the anteroposterior analysis of the tear. This study shows the limits of endoscopic assessment of full-thickness rotator cuff tears. It illustrates the need for an adequate arthroscopic technique with a thorough knowledge of normal and pathological anatomy of the rotator cuff.

PURPOSE: The initial report from the Programme Action Concertée Sein (PACS) PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS) and overall survival (OS) rates with the sequential administration of docetaxel after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast cancer. We evaluate here the impact of this regimen at 8 years. PATIENTS AND METHODS: Between June 1997 and March 2000, a total of 1,999 patients (age <65) with localized, resectable, non-pretreated, unilateral breast cancer were randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21 days. Radiotherapy was mandatory after conservative surgery and tamoxifen was given for 5 years to hormone receptor (HR)-positive patients. Five-year DFS was the trial's main endpoint. Updated 8-year survival data are presented. RESULTS: With a median follow-up of 92.8 months, 639 patients experienced at least one event. A total number of 383 deaths were registered. Eight-year DFS rates were 65.8% with FEC alone and 70.2% with FEC-D. OS rates at 8 years were 78% with FEC alone and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse and a 25% reduction in the relative risk of death in favor of FEC-D. Significant relative risk reductions were observed in the HR-positive, HER2-positive, and Ki67 ≥20% subpopulations. CONCLUSION: Benefits for DFS and OS rates with the sequential FEC-D regimen are fully confirmed at 8 years.

PURPOSE OF THE STUDY: The aim of this study was to evaluate the anatomical and technical limits of endoscopic rotator cuff repair. Anatomical results were also compared with functional assessment of the shoulder. MATERIAL AND METHODS: A multicentric serie of 87 patients presenting a full thickness rotator cuff tear repaired endoscopically was retrospectively reviewed at 25.4 months (mean) post surgery. Limits of the surgical technique were studied in correlation with functional results and anatomic radiographic evaluation (arthroscans in 93 p. 100). RESULTS: Anatomical repair (normal thickness and no contrast in the subacromial space on arthroscan) was achieved in 83 p. 100 of the rotator cuffs with limited damage to the frontal part of the supra spinatus tendon. This percentage fell to 57.8 p. 100 in case of posterior extension of the tear to the supra spinatus tendon and further dropped to 40.8 p. 100 in case of retraction to the apex of the humeral head. Functional outcome evaluated with the Constant score was strongly related to the radiographic cuff condition (p <0.05). For distal and anterior tears of the supra spinatus tendon, the Constant score at revision was 89.8 points in cases with anatomic repair at revision. This score fell to 75 when the rotator cuff tear was evidenced radiographically (p <0.0001). For tears involving the entire supra spinatus tendon repaired by arthroscopy, the functional difference at revision was 8 points on the Constant scale. Objective and subjective analysis of the surgical procedure identified significant peroperative elements predictive of clinical and anatomical outcome (difficult reduction, p <0.05; subjective degree of solidity, p <0.0001; anatomical aspect of the repaired cuff, p <0.05). DISCUSSION: A comparison of our findings with data on equivalent lesions reported in the literature suggests that endoscopic surgery for rotator cuff tears offers both functional and anatomic results equivalent to those achieved with conventional open surgery. This assumes that the surgical procedure is carried out by surgeons experienced in shoulder arthroscopy who can precisely gauge the posterior/anterior extension of the tears and the limits of the surgical technique.

Meeting abstracts TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1 tumor-associated antigen and interleukin-2. A previous study showed that a normal baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16+CD56+CD69+) might be a predictive biomarker for TG4010 efficacy

Abstract Background Numerous studies have documented modifications in vector orientation behavior, settling and feeding behavior, and/or fecundity and survival due to virus infection in host plants. These alterations are often expected to enhance virus transmission, which has led to the hypothesis that such effects are vector manipulations by the virus. However, until now, the gene expression changes correlating with these effects and indicative of modified vector pathways and mechanisms are mostly unknown. Results Transcriptome profiling of Myzus persicae aphids feeding on turnip yellows virus (TuYV) and cauliflower mosaic virus (CaMV) infected Arabidopsis thaliana and Camelina sativa revealed a substantial proportion of commonly deregulated genes, amongst them many with general functions in plant-virus-aphid interactions. We identified also aphid genes specifically deregulated by CaMV or TuYV infection, which might be related to the viral transmission mode. Furthermore, we observed strong host-specific differences in the gene expression patterns with plant virus infection causing more deregulations of aphid genes on A. thaliana than on C. sativa , likely related to the differences in susceptibility of the plant hosts to these viruses. Finally, stress-related aphid genes were downregulated in M. persicae on both infected plants, regardless of the virus. Conclusions TuYV, relying on the circulative persistent mode of transmission, tended to affect developmental genes. This could increase the proportion of alate aphids, but also affect their locomotion, neuronal activity, and lifespan. CaMV, using the non-circulative non-persistent mode of transmission, had a strong impact on feeding-related genes and in particular those related to salivary proteins. In general, these transcriptome alterations targeted pathways that seem to be particularly adapted to the transmission mode of the corresponding virus and could be evidence of vector manipulation by the virus.

The need of biomarkers of Alzheimer's disease (AD) is essential for the development of new therapeutic agents. Such biomarkers should be easily accessible (ie peripheral), equally significant in humans and in animal models and possibly predictive. We have developed a method based on the use of a specific fluorescent probe, which detect bound A-beta 1-42 on cellular membranes. This method was successfully applied to fresh red blood cells from transgenic animal models of AD. The present work was aimed at testing this new biomarker on human patients and healthy volunteers. A clinical study was conducted with 131 participants. Measurements were performed on 68 Alzheimer's disease patients (AD); (14 males and 54 females) and 37 healthy controls (HC) (6 males and 31 females) aged > 80. Additionally we performed measurements on 20 patients suffering from multiple sclerosis (35 years). A new fluorescent probe specific for Abeta1-42 was used to evaluate the amount of bound Abeta1-42 on fresh red blood cells. After fluorescence recording and spectral deconvolution, a spectral index was calculated, which is indicative of the peptide amount bound to the cells. This spectral index value enabled us to significantly distinguish AD samples from other samples with a sensitivity of 83% and a specificity of 82.2%. A slight correlation with age was found for the spectral index value within the AD population. The test was not altered by the drug treatment received by the AD patients. No significant change was observed in RBC from patients suffering from multiple sclerosis as compared to healthy volunteers. The present results are similar to those obtained on animal models. Our protocol appears to be efficient in detecting AD patients and might by used as a confirmatory parameter for a clinical diagnosis. It is not invasive, rapid and should be cost effective. Its predictive value remains to be assessed. However the fact that it is equally efficient on patients and on animal models already suggests that it should be an essential tool for the preclinical development of disease modifier therapeutic agents.

ABSTRACT Background Socioeconomic deprivation (SED) is increasingly recognized as a key determinant of morbidity and mortality among patients receiving hemodialysis. However, most prior studies have relied on area-level socioeconomic indicators and have been conducted outside of Europe. Objective To assess whether individual-level socioeconomic status, measured using the EPICES score, influences healthcare quality and patient behaviors in adults undergoing maintenance hemodialysis in northeastern France. Methods This multicenter observational study was conducted across five dialysis units. Adult patients with end-stage renal disease receiving hemodialysis for ≥3 months were enrolled. The EPICES score was used to assess individual SED, and patients were stratified into deprived (P+) and non-deprived (P−) groups based on the median score. Clinical, biochemical, and behavioral variables were compared between groups. Results A total of 401 patients were included (mean age 68.5 years; 60% male). The median EPICES score was 33.1 (mean 35.8 ± 18.9). Compared with P − patients, P + patients had a significantly longer dialysis vintage (76.3 vs. 73.9 months, p = .002), higher normalized protein catabolic rate (nPCR; 1.28 vs. 1.06 g/kg/day, p = .007), higher CRP concentrations (14.3 ± 4.1 vs. 9.56 ± 0.8 mg/L, p &amp;lt; .02 ), and greater smoking prevalence (34% vs. 15%, p = .004). No significant differences were observed in albumin and hemoglobin levels, erythropoietin (EPO) dosing, or the frequency of missed dialysis sessions. The CRP × P + interaction on nPCR was significant, suggesting that systemic inflammation could modify the association between deprivation and protein catabolism. Conclusion Individual-level SED was associated with differences in health behaviors but not in the quality of physician-driven dialysis care. These findings challenge the notion that deprived patients inherently receive lower-quality clinical care and emphasize the need for targeted strategies that address patient-dependent behavioral factors.

Abstract After FASE-CPHG in 2016 which had included 1502 patients with severe asthma, we are presenting another observational, cross-sectional and descriptive study of patients with severe asthma followed in French nonacademic hospitals. The main objective of the study was to present an updated description of severe asthma. Methods Since 03/01/2022, adults patients with severe asthma (GINA 5) met in a French nonacademic hospital have been included. Findings: Out of 1031 screened patients, 1002 were included and 970 analyzed, comprizing 643 women (66%) and 327 men (34%) with a mean age 54.5 years old (+/-15.8). Among them, 553 (57%) presented an ENT disease including 258 (26.6%) with nasal polyposis. Other comorbidities were: GERD (35%), obesity (32%), high blood pressure (25 %) OSAS (17%) and diabetes (12.7%), Samter's triad 8.1%. Anxiety was present in 26.5% of patients and depression in 34 patients (10.7%). The median FEV1 was 74.7% (+/-22.5) of the predicted value and less than 60% in 25% of patients. Allergologic assessment by prick-tests was performed in 605 patients (62%) and positive in 392 cases (67%). Blood eosinophils count was measured in 85.5% of cases with a mean value of 601 (+/-653) G/L and a median value of 450 G/L. The mean number of exacerbations on the last 12 months was 2.1 +/-3.5. 40% of patients were frequent exacerbators with 2 or more episodes. Concerning the treatments, 93% received a combination CSI/LABA with a mean dose of CSI at 1453 ug/d (+/-1521), 62.5% a LAMA and 12% a long term oral corticosteroids with a mean daily dose of 10 mg and an annual cumulative dose of 3332 mg. Related to exacerbations, 29% received a short course of CSO during the last 12 months (cumulative dose = 880 +/-1138 mg). 11% of patients received a low dose of ICS, 8% a medium dose and 81% a high dose. 83% of patients were treated with biologics: anti-IgE: 35%, anti-IL-5: 24%, anti-IL-5R: 22% and anti-IL-4/IL-13: 18%. According to the Girerd's observance score, treatment compliance was good for 31.6% of patients, average for 56.4% and poor for 12% of patients. Despite all these treatments, asthma was found as uncontrolled in 62%, moderately controlled in 28.6% and well controlled in only 11.7% of patients. Conclusion With this large population of more than 1000 patients, FASE 2 – CPHG will make it possible to refine the description of patients with severe asthma followed in French non-academic hospitals.

Abstract BACKGROUND Primary cerebral T-cell lymphomas are very rare and remain poorly known as opposed to diffuse large B-cell lymphomas (DLBCL) that account for more than 90% of all primary central nervous system lymphomas (PCNSL). The aim of the present study was to describe the characteristics of primary T-cell lymphomas, as well as their treatment and outcomes. MATERIAL AND METHODS We retrospectively selected from the French LOC (“Lymphomes oculo-cérébraux”) database the cases of primary T-cell lymphomas diagnosed between January 2011 to December 2023. RESULTS Of the 2966 patients diagnosed with PCNSL between January 2011 and February 2024, 16 patients (0.54%), including 9 men, were diagnosed with primary T-cell lymphoma. Their median age was 60 years [25-80], their median KPS was 70 [20-90]. The mean delay between first symptoms and diagnosis was 78 days [13-365]. Four patients had a history of auto-immune disease and 2 patients were under immunosuppressive therapy. Six patients harboured a classical aspect of brain lymphoma on MRI (tumor with intense and homogeneous contrast enhancement). In ten patients, the MRI presentation was atypical and other diagnoses were suspected before brain biopsy: high-grade gliomas in six immunocompetent patients with necrotic/hemorrhagic lesions, cerebral vasculitis in 2 patients, gliomatosis cerebri in one patient and cerebral metastasis in one patient. The histological diagnosis was NOS peripheral T-cell lymphoma in 8 patients, anaplastic large-cell lymphoma in 4 patients (2 ALK negative, 1 ALK positive, 1 undetermined), EBV-negative NK-T-cell in 1 patient, T-cell lymphomatosis cerebri in 1 patient (2 missing data). Clonality assessment by PCR found a TCR clonal rearrangement in 5/7 cases.Fifteen of 16 patients were treated with high dose methotrexate-based chemotherapy as induction therapy in first-line treatment. Six patients received intensive chemotherapy with autologous stem cell transplantation during their follow-up Nine patients relapsed, either during first-line treatment (N=3) or during the follow-up after treatment (N=6). The median follow-up was 32 months. The 2-year PFS rate was 46% (95% CI: 26-81) The 2-year OS rate was 67% (46-96) Conclusion: T-cell lymphoma represents a rare and severe form of PCNSL. It often occurs in patients with a different background than in DLBCL: younger patients, history of autoimmune disease or immunosuppression. The diagnosis can be challenging as the radiological presentation is most often atypical, often mimicking high grade gliomas or vasculitis, leading to a delayed diagnosis.

Systematic screening for hepatitis C virus (HCV) by serology once in a lifetime is recommended by the French Association for the Study of the Liver, but not by the French National Authority for Health. Screening focused on subjects aged over 40 years would seem more appropriate, as the prevalence of hepatitis C increases with age. The aim of this study was to assess the feasibility (number of serologies proposed) and acceptability (number of serologies performed) of HCV screening prior to endoscopy in people aged 40 years and over seen in gastroenterology consultations in non-university hospitals; and to determine whether the prevalence after age 40 is higher than in the general population (0.86%). As of 1 June 2023, 490 patients were included in eight different hospitals in six regions of metropolitan France; 97.4% of patients accepted the prescription of HCV serology and 97.6% of prescribed serologies were performed; 55.5% were men and 44.4% women with a mean age of 58 years (range, 40-90). The HCV serology positivity rate was 6% (29 patients). No previous HCV serology was known. Risk exposures associated with positive HCV serology were drug use in 19 patients, a history of transfusion in six patients and origin from an endemic country in five patients; 90% of positive serologies concerned men and the mean age was 65 years (range, 49-85). Mean hepatic elastometry was 8.7 kPa; 11 out of 28 patients tested had a positive HCV viral load and were treated. Systematic screening for hepatitis C after the age of 40 years and before digestive endoscopy is feasible, well accepted and enables a high number of patients to be managed.

ABSTRACT Downy mildew caused by the oomycete Plasmopara viticola is one of the most important diseases affecting grapevine. Resistant varieties are an environmentally-friendly tool to control grapevine downy mildew. Efficient breeding for durable resistance requires knowledge of the underlying mechanisms. Here we aimed at identifying the molecular basis of Rpv2 , a gene for extreme resistance to downy mildew derived from Vitis rotundifolia , and at characterizing its effect on pathogen development. Individuals from two populations segregating for Rpv2 were evaluated for resistance to downy mildew and genotyped. Following genetic mapping, markers flanking Rpv2 were used to screen new populations and identify recombinant individuals. Sequencing of recombinants and in silico chromosome painting was used to reduce the interval containing Rpv2 . Comparative genomics inside the Vitaceae , involving de novo assembly of the V. rotundifolia Regale genome, allowed narrowing-down the list of candidate genes. We restrict Rpv2 to a 250 kb genomic region that contains two resistance genes of the NLR type. Comparative genomics analyses could not find orthologs of both NLRs in the other Vitis species studied. We also show that Rpv2 -mediated resistance leads to pathogen arrest early in the infection cycle. Our results show that Rpv2 belongs to the NLR family of resistance genes, contributing thus to understand the potential and risks of its use in breeding programs and suggesting that combining NLR-type genes may lead to durable resistance KEY MESSAGE The Rpv2 locus for extreme resistance to grapevine downy mildew is mapped to a 250 kb genomic region containing two NLR-type genes specific to V. rotundifolia .

Background: Hepatocellular carcinoma (HCC) is the most common hepatic malignancy and is one of the most prevalent cancers worldwide. The prognosis of late-stage HCC remains poor. The ImBrave 150 trial successfully demonstrated that overall survival (OS) and progression-free survival (PFS) was improved among patients treated with atezolizumab combined with bevacizumab (AB) compared with patients treated with sorafenib. Real-world data are essential to assess the safety and efficacy of new therapies in HCC, given patients' fragility and the heterogeneity of underlying liver diseases. Objective: The primary objective of this study was to evaluate the OS and PFS of patients with locally advanced or metastatic HCC treated with atezolizumab combined with bevacizumab. The secondary objective was to conduct subgroup analyses to further examine how the effects of the combination treatment differ based on Child‒Pugh scores, prior local treatment, and alpha-fetoprotein (AFP) levels. Methods: We conducted a multicentric retrospective study. All patients with confirmed locally advanced or metastatic HCC treated with atezolizumab combined with bevacizumab between January 2021 and December 2023 were included. Results: Seventy patients were included. A total of 76% presented with cirrhosis, among which 85% had Child‒Pugh class A cirrhosis. The cirrhosis cases were mostly nonviral (85.7%). The median OS was 19 months (95% CI: 15-NA), and the median PFS was 6.7 months (95% CI: 4.7-14.2 months). The secondary analysis revealed a statistically significant difference in OS between patients with Child‒Pugh class A cirrhosis and those with Child‒Pugh class B cirrhosis, with median OS durations of 18.9 months (95% CI: 16.9-NA) and 6.0 months (95% CI: 1.5-NA), respectively (p = 0.03). However, the retrospective design and the lack of a control group represent important limitations. Conclusion: Our real-life study yielded OS and PFS durations similar to those reported in the ImBrave 150 trial.

Abstract Background Vitis vinifera L. is the most cultivated grapevine species worldwide. Erysiphe necator Sch., the causal agent of grape powdery mildew, is one of the main pathogens affecting viticulture. V. vinifera has little or no genetic resistance against E. necator and the grape industry is highly dependent on agrochemicals. Some Caucasian V. vinifera accessions have been reported to be resistant to E. necator and to have no genetic relationship to known sources of resistance to powdery mildew. The main purpose of this work was the study and mapping of the resistance to E. necator in the Caucasian grapes ‘Shavtsitska’ and ‘Tskhvedianis tetra’.ResultsThe Caucasian varieties ‘Shavtsitska’ and ‘Tskhvedianis tetra’ showed a strong partial resistance to E. necator which segregated in two cross populations: the resistant genotypes delayed and limited the pathogen mycelium growth, sporulation intensity and number of conidia generated. A total of 184 seedlings of ‘Shavtsitska’ x ‘Glera’ population were genotyped through the Genotyping by Sequencing (GBS) technology and two high-density linkage maps were developed for the cross parents. The QTL analysis revealed a major resistance locus, explaining up to 80.15% of the phenotypic variance, on ‘Shavtsitska’ linkage group 13, which was associated with a reduced pathogen infection as well as an enhanced plant necrotic response. The genotyping of 105 Caucasian accessions with SSR markers flanking the QTL revealed that the resistant haplotype of ‘Shavtsitska’ was shared by ‘Tskhvedianis tetra’ and a total of 24 Caucasian grape varieties, suggesting a widespread presence of this resistance in the surveyed germplasm. The uncovered QTL was mapped in the region where the Ren1 gene of resistance to E. necator , identified in the V. vinifera ‘Kishmish vatkana’ and related grapes of Central Asia, is located. The genetic analysis conducted revealed that the Caucasian grapes in this study exhibit a resistant haplotype different from that of Central Asian grape accessions.ConclusionsThe QTL isolated in ‘Shavtsitska’ and present in the Caucasian V. vinifera varieties could be a new candidate gene of resistance to E. necator to use in breeding programmes. It co-localizes with the Ren1 locus but shows a different haplotype from that of grapevines of Central Asia. We therefore consider this gene, named Ren1-2 , a member of a cluster of R genes, of which the region is rich, and linked with, or possibly allelic, to the Ren1 .

<strong>Abstract</strong> There is growing evidence that plant viruses manipulate their hosts and vectors in ways that increase transmission. However, to date only few viral components underlying these phenomena have been identified. Here we show that cauliflower mosaic virus (CaMV) protein P2 modifies the feeding behavior of its aphid vector. P2 is necessary for CaMV transmission because it mediates binding of virus particles to the aphid mouthparts. We compared aphid feeding behavior on plants infected with the wild-type CaMV strain B-JI or with a deletion mutant strain, B-JIΔP2, which does not produce P2. Only aphids probing B-JI infected plants doubled the number of test punctures during the first plant contact, indicating a role of P2. Membrane feeding assays with purified P2 and virus particles confirmed that these viral products alone are sufficient to cause the changes in aphid probing. The behavior modifications were not observed on plants infected with a CaMV mutant expressing P2Rev5, unable to bind to the mouthparts. These results are in favor of a parasite manipulation, where attachment of P2 to a specific region in the aphid stylets – the acrostyle – exercises a direct effect on vector behavior at a crucial moment, the first vector contact with the infected plant, which is essential for virus acquisition. <strong>Significance</strong> Some pathogens including plant viruses manipulate vectors to optimize transmission. Some modifications are direct, i.e. uptake of virus compounds changes vector behaviors. Direct effects have been reported for viruses that are internalized by their vectors and therefore interact strongly with the vector from within. Here we show that contact of a virus protein with the vector’s exterior mouthparts suffices to induce a direct effect: Binding of CaMV protein P2 to aphid stylets during test punctures modifies probing activity instantly, thereby facilitating virus transmission. This reveals that CaMV prepares for transmission already within the plant host, by presenting P2. This minimizes vector implication and could explain the broad vector range of CaMV and other non-circulative viruses.

&amp;lt;p&amp;gt;The term Organic Waste Products (OWPs) encompasses a wide range of byproducts such as manure, sewage sludge or green waste compost. The use of OWPs impacts soil quality and functioning, agricultural yields, carbon (C) sequestration, biogeochemical cycles of nutrients like nitrogen (N) or phosphorus, and organic matter (OM) dynamics. These impacts likely depend on the considered OWP.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Taking advantage of 3 mid to long-term experimental trials (6 to 20 years) located in the Northern part of France (Paris region; Brittany; Alsace), we investigated the impact of 16 different OWPs on C content and stability. To do so, surface soil samples from replicated plots amended with the different OWPs used either alone or in addition with mineral N fertilization and appropriated control treatments were analyzed using Rock-Eval 6&amp;amp;#174; thermal analyses. Samples taken up at the onset of the experiment and after 6, 18 and 20 years for the 3 sites respectively were analyzed. It resulted in the analyses of 248 different samples whose Rock-Eval 6&amp;amp;#174; (RE6) signature can be used as a proxy for soil organic carbon (SOC) biogeochemical stability. In particular, we determined 2 RE6 parameters that were related to SOC biogeochemical stability in previous studies (e.g. Barr&amp;amp;#233; et al., 2016): HI (the amount of hydrogen-rich effluents formed during the pyrolysis phase of RE6; mgCH.g&amp;lt;sup&amp;gt;-1&amp;lt;/sup&amp;gt; SOC), and T50 CO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; oxidation (the temperature at which 50% of the residual organic C was oxidized to CO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; during the RE6 oxidation phase; &amp;amp;#176;C). We also computed the amount of centennially stable SOC from RE6 parameters using the model developed in C&amp;amp;#233;cillon et al. (2018). &amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Our results showed that no clear effect of OWPs addition can be established for the youngest site (6 years). On the contrary, OWPs amendments had a clear effect on SOC quantity and quality at the sites having experienced 18 and 20 years of OWPs addition. For these sites, OWPs amendments increased SOC content, decreased SOC thermal stability (T50 CO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; oxidation) and increased the Rock-Eval 6&amp;amp;#174; Hydrogen Index (HI) compared to control plots. OWPs amendments tended to increase slightly the amount of centennially stable SOC at the sites having experienced 20 years of repeated OWPs application. Our results suggest that if OWPs addition does increase SOC content, at least in the long run, the majority of this additional SOC is labile and may be quickly lost if OWPs additions are stopped.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;References:&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Barr&amp;amp;#233; P., Plante A.F., C&amp;amp;#233;cillon L., Lutfalla S., Baudin F., Bernard S., Christensen B.T., Eglin T., Fernandez J.M., Houot S., K&amp;amp;#228;tterer T., Le Guillou C., Macdonald A., van Oort F. &amp;amp; Chenu C. (2016) The energetic and chemical signatures of persistent soil organic matter. Biogeochemistry, 130: 1-12.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;C&amp;amp;#233;cillon L., Baudin F., Chenu C., Houot S., Jolivet R., K&amp;amp;#228;tterer T., Lutfalla S., Macdonald A.J., van Oort F., Plante A.F., Savignac F., Souc&amp;amp;#233;marianadin L.N. &amp;amp; Barr&amp;amp;#233; P. (2018) A model based on Rock-Eval thermal analysis to quantify the size of the centennially persistent organic carbon pool in temperate soils. Biogeosciences, 15, 2835-2849.&amp;lt;/p&amp;gt;

The need of biomarkers of Alzheimer's disease (AD) is essential for the development of therapeutic agents. Such biomarkers should be easily accessible (ie peripheral), equally significant in humans and in animal models and possibly predictive. We have developed a method based on the use of a specific fluorescent probe, which detects bound A-beta 1-42 on cellular membranes. This method was successfully applied to fresh red blood cells from transgenic animal models of AD and blood samples from AD patients. A new fluorescent probe specific for Abeta1-42 was used to evaluate the amount of bound Abeta1-42 on fresh red blood cells. A clinical study was conducted with 131 participants. Measurements were performed on samples from 68 Alzheimer's disease patients (AD) and 37 healthy controls (HC) aged > 80. Additionally we performed measurements on 20 patients suffering from multiple sclerosis. The same protocol was also used on red blood cells from wild type and transgenic TASTPM mice aged 4 or 14 month. No significant difference in the value of the spectral index between wild type and transgenic TASTPM mice aged 4 month was observed indicating that the test was negative before the development of the pathology in the transgenic model. In mice aged 14 months, when the pathology almost completely developed, our measurement was able to distinguish wild type from transgenic mice. Similar results were obtained on human samples: our test displayed a specificity of 82 % and a sensitivity of 83 % when AD patients were compared to Healthy controls and other neurodegenerative diseases. The treatment of the patients with classical symptomatic agents did not alter our measurement For the first time we describe a peripheral biomarker directly related to the pathology pathway and which is equally efficient in human and in animal models. This might be an essential tool for developing new disease modifiers drugs against AD.

<strong>Abstract</strong> There is growing evidence that plant viruses manipulate their hosts and vectors in ways that increase transmission. However, to date only few viral components underlying these phenomena have been identified. Here we show that cauliflower mosaic virus (CaMV) protein P2 modifies the feeding behavior of its aphid vector. P2 is necessary for CaMV transmission because it mediates binding of virus particles to the aphid mouthparts. We compared aphid feeding behavior on plants infected with the wild-type CaMV strain B-JI or with a deletion mutant strain, B-JIΔP2, which does not produce P2. Only aphids probing B-JI infected plants doubled the number of test punctures during the first contact with the plant, indicating a role of P2. Membrane feeding assays with purified P2 and virus particles confirmed that these viral products alone are sufficient to cause the changes in aphid probing. The behavior modifications were not observed on plants infected with a CaMV mutant expressing P2Rev5, unable to bind to the mouthparts. These results are in favor of a virus manipulation, where attachment of P2 to a specific region in the aphid stylets – the acrostyle – exercises a direct effect on vector behavior at a crucial moment, the first vector contact with the infected plant, which is essential for virus acquisition.