Search

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe’s largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017–2019. We assessed risk factors of 1-year recurrence using Fine–Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32–6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50–3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Whole orchard recycling (WOR) is an emerging practice in perennial cropping systems and is an alternative to open or cogeneration burning. It is an orchard removal practice that incorporates large amounts of woody biomass back into the soil system. In this study, we utilized a soil hydrological model (HYDRUS-1D) to evaluate the seasonal effects of WOR on water movement and nitrogen (N) retention for a newly established almond orchard on a typical sandy loam soil in the Central Valley of California. Soil moisture and N content were monitored across the first five growing seasons from 2018 to 2022. The model was able to track seasonal moisture fluctuation nicely compared to observed data. Additionally, an increase in soil moisture was measured in the WOR treatments in surface soil (i.e., 0- to 15-cm depths) where biomass was incorporated, and N leaching was reduced when compared to the unamended control. Simulations suggest that with WOR, irrigation can be reduced by up to 20 % during the tree establishment stage with minimal effect on root water uptake. This reduction in applied water can increase farm water use efficiency and reduce operational expenses, e.g., cost of water and pumping. Likewise, the reduction in N leaching observed in both predicted results and laboratory analysis can further cut farm capital costs, e.g., fertilization, and lessen orchard environmental impacts. Overall, results from our simulation show a positive effect of WOR on soil ecosystem services and can potentially be a profitable strategy for orchard turnover. The results have important implications in reducing groundwater nitrate contamination in irrigated agriculture in the Central Valley of California and applicable to most parts of Southwestern United States.

BackgroundThe geographic and temporal distributions of bacterial and fungal populations are poorly understood within the same wine grape cultivar. In this work, we describe the microbial composition from 'Pinot noir' must with respect to vintage, growing region, climate, and must chemistry across the states of California and Oregon, USA.Materials and methodsWe sampled 'Pinot noir' clone 667 clusters from 15 vineyards existing in a latitudinal gradient spanning nearly 1,200 km in California and Oregon for two vintages (2016 and 2017). Regions included five American Viticultural Areas (AVA). In order from southern California to Oregon, these AVAs were Santa Barbara, Monterey, Sonoma, Mendocino, and Willamette Valley. Uninoculated grape musts were subjected to 16S rRNA gene and ITS-1 amplicon sequencing to assess composition of microbial communities. We also measured grape maturity metrics. Finally, to describe regions by precipitation and growing degree days, we queried the Parameter-elevation Regressions on Independent Slopes Model (PRISM) spatial climate dataset.ResultsMost of the dominant bacterial taxa in must samples were in the family Enterobacteriaceae, notably the lactic acid bacteria or the acetic acid bacteria groups, but some, like the betaproteobacterial genus Massilia, belonged to groups not commonly found in grape musts. Fungal communities were dominated by Hanseniaspora uvarum (Saccharomycetaceae). We detected relationships between covariates (e.g., vintage, precipitation during the growing season, pH, titratable acidity, and total soluble solids) and bacterial genera Gluconobacter and Tatumella in the family Enterobacteraceae, Sphingomonas (Sphingomonodaceae), Lactobacillus (Lactobacillaceae), and Massilia (Oxalobacteraceae), as well as fungal genera in Hanseniaspora, Kazachstania, Lachancea, Torulaspora in the family Saccharomycetaceae, as well as Alternaria (Pleosporaceae), Erysiphe (Erysiphaceae), and Udeniomyces (Cystofilobasidiaceae). Fungal community distances were significantly correlated with geographic distances, but this was not observed for bacterial communities. Climate varied across regions and vintages, with growing season precipitation ranging from 11 mm to 285 mm and growing degree days ranging from 1,245 to 1,846.DiscussionWe determined that (1) bacterial beta diversity is structured by growing season precipitation, (2) fungal beta diversity reflects growing season precipitation and growing degree days, and (3) microbial differential abundances of specific genera vary with vintage, growing season precipitation, and fruit maturity metrics. Further, the correlation between fungal community dissimilarities and geographic distance suggests dispersal limitation and the vineyard as a source for abundant fungal taxa. Contrasting this observation, the lack of correlation between bacterial community dissimilarity and geographic distance suggests that environmental filtering is shaping these communities.

Zebra mussel (ZM), Dreissena polymorpha, commonly used as a sentinel species in freshwater biomonitoring, is now in competition for habitat with quagga mussel (QM), Dreissena rostriformis bugensis. This raises the question of the quagga mussel’s use in environmental survey. To better characterise QM response to stress compared with ZM, both species were exposed to cadmium (100 µg·L−1), a classic pollutant, for 7 days under controlled conditions. The gill proteomes were analysed using two-dimensional electrophoresis coupled with mass spectrometry. For ZM, 81 out of 88 proteoforms of variable abundance were identified using mass spectrometry, and for QM, 105 out of 134. Interestingly, the proteomic response amplitude varied drastically, with 5.6% of proteoforms of variable abundance (DAPs) in ZM versus 9.4% in QM. QM also exhibited greater cadmium accumulation. Only 12 common DAPs were observed. Several short proteoforms were detected, suggesting proteolysis. Functional analysis is consistent with the pleiotropic effects of the toxic metal ion cadmium, with alterations in sulphur and glutathione metabolisms, cellular calcium signalling, cytoskeletal dynamics, energy production, chaperone activation, and membrane events with numerous proteins involved in trafficking and endocytosis/exocytosis processes. Beyond common responses, the sister species display distinct reactions, with cellular response to stress being the main category involved in ZM as opposed to calcium and cytoskeleton alterations in QM. Moreover, QM exhibited greater evidence of proteolysis and cell death. Overall, these results suggest that QM has a weaker stress response capacity than ZM.

Plant-microbe interactions in the rhizosphere influence rates of organic matter mineralization and nutrient cycling that are critical to sustainable agricultural productivity. Agricultural intensification, particularly the introduction of synthetic fertilizer in the USA, altered the abundance and dominant forms of nitrogen (N), a critical plant nutrient, potentially imposing selection pressure on plant traits and plant-microbe interactions regulating N cycling and acquisition. We hypothesized that maize adaptation to synthetic N fertilization altered root functional traits and rhizosphere microbial nutrient cycling, reducing maize ability to acquire N from organic sources. Six maize genotypes released pre-fertilizer (1936, 1939, 1942) or post-fertilizer (1984, 1994, 2015) were grown in rhizoboxes containing patches of 15N-labelled clover/vetch residue. Multivariate approaches did not identify architectural traits that strongly and consistently predicted rhizosphere processes, though metrics of root morphological plasticity were linked to carbon- and N-cycling enzyme activities. Root traits, potential activities of extracellular enzymes (BG, LAP, NAG, urease), abundances of N-cycling genes (amoA, narG, nirK, nirS, nosZ) and uptake of organic N did not differ between eras of release despite substantial variation among genotypes and replicates. Thus, agricultural intensification does not appear to have impaired N cycling and acquisition from organic sources by modern maize and its rhizobiome. Improved mechanistic understanding of rhizosphere processes and their response to selective pressures will contribute greatly to rhizosphere engineering for sustainable agriculture.

Salam Abbara,1,2 Didier Guillemot,1– 3 Salma El Oualydy,4 Maeva Kos,4 Cécile Poret,5 Stéphane Breant,5 Christian Brun-Buisson,1,2 Laurence Watier1,2 1Anti-Infective Evasion and Pharmacoepidemiology Team, Inserm, UVSQ, University Paris-Saclay, CESP, Montigny-Le-Bretonneux, France; 2Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE), University Paris Cité, Paris, France; 3Public Health, Medical Information, Clinical Research, AP-HP, University Paris Saclay, Le Kremlin-Bicêtre, France; 4Plateforme des données de santé - Health Data Hub, Paris, France; 5AP-HP, Direction des Systèmes d’Information, Pôle Innovation et Données, Paris, FranceCorrespondence: Salam Abbara, Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE) Unit, 25-28 rue du Docteur Roux, Paris, 75015, France, Tel +33 1 45 68 80 00, Email salam.abbara@gmail.comPurpose: Antibiotic-resistant bacteremia is a leading global cause of infectious disease morbidity and mortality. Clinical data warehouses (CDWs) allow for the secure, real-time coupling of diverse data sources from real-world clinical settings, including care-based medical-administrative data and laboratory-based microbiological data. The main purpose of this study was to assess the contribution of CDWs in the epidemiological study of antibiotic resistance by constructing a database of bacteremia patients, BactHub, and describing their main clinico-microbiological features and outcomes.Patients and Methods: Adult patients with bacteremia hospitalized between January 1, 2016 and December 31, 2019 in 14 acute care university hospitals from the Greater Paris area were identified; their first bacteremia episode was included. Data describing patients, episodes of bacteremia, bacterial isolates, and antimicrobial resistance were structured.Results: Among 29,228 patients with bacteremia, 41% of episodes were community-onset (CO) and 59% were hospital-acquired (HA). Thirty-day and ninety-day mortality rates were 15% and 20% in CO episodes, and 18% and 36% in HA episodes. Overall resistance rates were high, including third-generation cephalosporin resistance among Klebsiella pneumoniae (CO 21%, HA 37%) and Escherichia coli (CO 13%, HA 17%), and methicillin resistance among Staphylococcus aureus (CO 11%, HA 14%). Annual incidence rates increased significantly from 2017 to 2019, from 20.0 to 20.9 to 22.1 stays with bacteremia per 1000 stays (p < 0.0001).Conclusion: The Bacthub database provides accurate clinico-microbiological data describing bacteremia across France’s largest hospital group. Data from Bacthub may inform surveillance and the clinical decision-making process for bacteremia patients, including choice of antimicrobial therapy. The database also offers opportunities for research, including analysis of hospital care pathways and significant patient outcomes such as mortality and recurrence of infection.Keywords: data warehousing, bacteremia, drug resistance, microbial, anti-bacterial agents, mortality, incidence

Ornamental production in the United States spans an estimated 267,000 ha and uses approximately 169,000 m3 of water yearly. Ornamental growers, particularly those with air-closed systems, are interested in implementing reduced irrigation technologies such as sensor-controlled irrigation systems to improve water use efficiency in response to water scarcity. To evaluate phytobiome impacts, we utilized an Illumina metabarcoding approach to characterize changes in fungal and oomycete rhizosphere communities of commercially grown poinsettia, complementing previous studies of single-pathogen impacts. Minor reductions (from 54 to 50% volumetric water content [VWC]) did not have large effects on rhizosphere fungal community structure but shifts in plant health status (symptomatic to asymptomatic) correlated with shifts in fungal diversity and evenness, with an increased abundance of several taxa, including Plectosphaerella cucumerina and Fusarium spp., in symptomatic plants. Further reductions in irrigation (45, 35, and 25% VWC) did not affect overall fungal community composition but the lowest VWC increased the abundance of potential root rot pathogens such as Phoma multirostrata and Plectosphaerella cucumerina. Reduced irrigation volumes decreased oomycete diversity and abundance of several known pathogens in the Phytophthora genus. Addition of a bacterial product (Companion) with putative pathogen-suppressive and drought-tolerance enhancing effects had no influence on fungal community composition or abundance but did increase abundance of some oomycete species at 45% VWC. This study shows that adoption of reduced irrigation may have greater effects on fungal versus oomycete taxa in the system, with consistent patterns of fungal enhancement, including putative fungal pathogens and beneficial organisms, and oomycete suppression.

ABSTRACT Infections are relatively rare following cutaneous surgical procedures, despite the potential for wound exposure to pathogens both during surgery and throughout the healing process. Although gut commensals are believed to reduce the risk of intestinal infections, an analogous role for skin commensals has not been described. In fact, the microbiome of normally healing surgical skin wounds has not yet been profiled using culture-independent techniques. We characterized the wound microbiome in 53 patients who underwent skin cancer surgery and healed without signs or symptoms of infection. A week after surgery, several bacterial species displayed significant differences in relative abundance when compared to control, nonoperated skin from the same patient. The relative abundance of the most common bacterium found on intact skin, Cutibacterium acnes, was reduced in wounds 5-fold. Staphylococcus aureus, a frequent cause of postoperative skin infections, was enriched 6.4-fold in clinically noninfected wounds, suggesting active suppression of pathogenicity. Finally, members of the Corynebacterium genus were the dominant organism in postoperative wounds, making up 37% of the average wound microbiome. The enrichment of these bacteria in normally healing wounds suggests that they might be capable of providing colonization resistance. Future studies focused on the biological and clinical significance of the wound microbiome may shed light on normal wound healing and potential therapeutic opportunities to mitigate infection risk. IMPORTANCE Commensal bacteria on skin may limit the ability of pathogenic bacteria to cause clinically significant infections. The bacteria on healing acute wounds, which might provide such a protective effect, have not been described using culture-independent approaches in the absence of antibiotics. We compare the microbiome of wounds a week after skin cancer removal surgery with intact skin from the same patient. We find that the potentially pathogenic species S. aureus is common on these healing wounds despite the absence of symptoms or signs of infection. We report that bacteria often considered as potential skin probiotics, including Staphylococcus epidermidis, do not reach high relative abundance in wound microbiomes. In contrast, specific members of the Corynebacterium genus, rarely associated with infections, were significantly enriched in healing wounds compared to intact skin. Future work is needed to see if Corynebacterium species or derivatives thereof could be employed to lower the risk of wound infection.

Abstract RhoH is an unusual member of the Rho family of small GTP‐binding proteins in that it lacks GTPase activity. Since the RhoH protein is constantly bound by GTP, it is constitutively active and controlled predominantly by changes in quantitative expression. Abnormal levels of RHOH gene transcripts have been linked to a range of malignancies including acute myeloid leukemia (AML). One of the hallmarks of AML is a block in the normal program of myeloid differentiation. Here we investigate how myeloid differentiation is controlled by the quantitative expression of RHOH. Our analysis demonstrates that increasingly mature myeloid cells express progressively lower levels of RHOH. However, as monocytic myeloid cells terminally differentiate into macrophages, RHOH expression is up‐regulated. This up‐regulation is not apparent in AML where myeloid differentiation is blocked at stages of low RHOH expression. Nevertheless, when the up‐regulation of RHOH is forced, then terminal macrophage differentiation is induced and the Cdc42 and Wnt intracellular signalling pathways are repressed. These results indicate that RHOH induction is a driver of terminal differentiation and might represent a means of effecting AML differentiation therapy. The potential of this therapeutic strategy is supported by forced up‐regulation of RHOH reducing the ability of AML cells to produce tumours in vivo.

Purpose: To assess the feasibility of a three-dimensional deep convolutional neural network (3D-CNN) for the general triage of whole-body FDG PET in daily clinical practice. Methods: An institutional clinical data warehouse working environment was devoted to this PET imaging purpose. Dedicated request procedures and data processing workflows were specifically developed within this infrastructure and applied retrospectively to a monocentric dataset as a proof of concept. A custom-made 3D-CNN was first trained and tested on an “unambiguous” well-balanced data sample, which included strictly normal and highly pathological scans. For the training phase, 90% of the data sample was used (learning set: 80%; validation set: 20%, 5-fold cross validation) and the remaining 10% constituted the test set. Finally, the model was applied to a “real-life” test set which included any scans taken. Text mining of the PET reports systematically combined with visual rechecking by an experienced reader served as the standard-of-truth for PET labeling. Results: From 8125 scans, 4963 PETs had processable cross-matched medical reports. For the “unambiguous” dataset (1084 PETs), the 3D-CNN’s overall results for sensitivity, specificity, positive and negative predictive values and likelihood ratios were 84%, 98%, 98%, 85%, 42.0 and 0.16, respectively (F1 score of 90%). When applied to the “real-life” dataset (4963 PETs), the sensitivity, NPV, LR+, LR− and F1 score substantially decreased (61%, 40%, 2.97, 0.49 and 73%, respectively), whereas the specificity and PPV remained high (79% and 90%). Conclusion: An AI-based triage of whole-body FDG PET is promising. Further studies are needed to overcome the challenges presented by the imperfection of real-life PET data.

Abstract Background Integrating genome-wide gene expression patient profiles with regulatory knowledge is a challenging task because of the inherent heterogeneity, noise and incompleteness of biological data. From the computational side, several solvers for logic programs are able to perform extremely well in decision problems for combinatorial search domains. The challenge then is how to process the biological knowledge in order to feed these solvers to gain insights in a biological study. It requires formalizing the biological knowledge to give a precise interpretation of this information; currently, very few pathway databases offer this possibility. Results The presented work proposes an automatic pipeline to extract automatically regulatory knowledge from pathway databases and generate novel computational predictions related to the state of expression or activity of biological molecules. We applied it in the context of hepatocellular carcinoma (HCC) progression, and evaluate the precision and the stability of these computational predictions. Our working base is a graph of 3383 nodes and 13,771 edges extracted from the KEGG database, in which we integrate 209 differentially expressed genes between low and high aggressive HCC across 294 patients. Our computational model predicts the shifts of expression of 146 initially non-observed biological components. Our predictions were validated at 88% using a larger experimental dataset and cross-validation techniques. In particular, we focus on the protein complexes predictions and show for the first time that NFKB1/BCL-3 complexes are activated in aggressive HCC. In spite of the large dimension of the reconstructed models, our analyses over the computational predictions discover a well constrained region where KEGG regulatory knowledge constrains gene expression of several biomolecules. These regions can offer interesting windows to perturb experimentally such complex systems. Conclusion This new pipeline allows biologists to develop their own predictive models based on a list of genes. It facilitates the identification of new regulatory biomolecules using knowledge graphs and predictive computational methods. Our workflow is implemented in an automatic python pipeline which is publicly available at https://github.com/LokmaneChebouba/key-pipeand contains as testing data all the data used in this paper.

Successive plantings of Prunus species produce suboptimal growth and yield in many California soils due to a poorly understood soilborne disease complex, Prunus replant disease (PRD). We explored the hypothesis that PRD is mediated by microbial taxa in roots of Nemaguard peach, a rootstock for almond and other stone fruits. In a greenhouse bioassay, portions of 10 replant soils were treated with fumigation or pasteurization or left untreated as a control before being planted with peach seedlings. Ten weeks after planting, seedlings were considered PRD-affected if their top fresh weights in the control were significantly reduced, compared to the weights in pasteurization and fumigation treatments; plants with equivalent top weights in all treatments were considered to be non-affected. The roots were washed from the soil, frozen, extracted for total DNA, and used for metabarcoding of rRNA gene amplicons from bacteria, fungi, and oomycetes. High-throughput amplicon sequencing revealed that root microbial community shifts resulted from preplant treatments, and specific taxa were associated with PRD induction among controls. Random forest (RF) analysis discriminated effectively between PRD-affected and non-affected root communities. Among the 30 RF top-ranked amplicon sequence variant (ASV) predictors, 26 were bacteria, two were oomycetes, and two were fungi. Among them, only Streptomyces scabiei, Steroidobacter denitrificans, Streptomyces bobili, and Pythium mamillatum had root abundances ≥5% that were either associated positively (former two ASVs) or negatively (latter two) with PRD. Thus, our findings were consistent with microbial mediation of PRD in roots and suggested taxa that may be involved in the mediation.

Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

During HIV-1 particle formation, the requisite plasma membrane curvature is thought to be solely driven by the retroviral Gag protein. Here, we reveal that the cellular I-BAR protein IRSp53 is required for the progression of HIV-1 membrane curvature to complete particle assembly. siRNA-mediated knockdown of IRSp53 gene expression induces a decrease in viral particle production and a viral bud arrest at half completion. Single-molecule localization microscopy at the cell plasma membrane shows a preferential localization of IRSp53 around HIV-1 Gag assembly sites. In addition, we observe the presence of IRSp53 in purified HIV-1 particles. Finally, HIV-1 Gag protein preferentially localizes to curved membranes induced by IRSp53 I-BAR domain on giant unilamellar vesicles. Overall, our data reveal a strong interplay between IRSp53 I-BAR and Gag at membranes during virus assembly. This highlights IRSp53 as a crucial host factor in HIV-1 membrane curvature and its requirement for full HIV-1 particle assembly.

Background The geographic and temporal distributions of bacterial and fungal populations are poorly understood within the same wine grape cultivar. In this work, we describe the microbial composition from ‘Pinot noir’ must with respect to vintage, growing region, climate, and must chemistry across the states of California and Oregon, USA. Materials and Methods We sampled ‘Pinot noir’ clone 667 clusters from 15 vineyards existing in a latitudinal gradient spanning nearly 1,200 km in California and Oregon for two vintages (2016 and 2017). Regions included five American Viticultural Areas (AVA). In order from southern California to Oregon, these AVAs were Santa Barbara, Monterey, Sonoma, Mendocino, and Willamette Valley. Uninoculated grape musts were subjected to 16S rRNA gene and ITS-1 amplicon sequencing to assess composition of microbial communities. We also measured grape maturity metrics. Finally, to describe regions by precipitation and growing degree days, we queried the Parameter-elevation Regressions on Independent Slopes Model (PRISM) spatial climate dataset. Results Most of the dominant bacterial taxa in must samples were in the family Enterobacteriaceae, notably the lactic acid bacteria or the acetic acid bacteria groups, but some, like the betaproteobacterial genus Massilia, belonged to groups not commonly found in grape musts. Fungal communities were dominated by Hanseniaspora uvarum (Saccharomycetaceae). We detected relationships between covariates (e.g., vintage, precipitation during the growing season, pH, titratable acidity, and total soluble solids) and bacterial genera Gluconobacter and Tatumella in the family Enterobacteraceae, Sphingomonas (Sphingomonodaceae), Lactobacillus (Lactobacillaceae), and Massilia (Oxalobacteraceae), as well as fungal genera in Hanseniaspora, Kazachstania, Lachancea, Torulaspora in the family Saccharomycetaceae, as well as Alternaria (Pleosporaceae), Erysiphe (Erysiphaceae), and Udeniomyces (Cystofilobasidiaceae). Fungal community distances were significantly correlated with geographic distances, but this was not observed for bacterial communities. Climate varied across regions and vintages, with growing season precipitation ranging from 11 mm to 285 mm and growing degree days ranging from 1,245 to 1,846. Discussion We determined that (1) bacterial beta diversity is structured by growing season precipitation, (2) fungal beta diversity reflects growing season precipitation and growing degree days, and (3) microbial differential abundances of specific genera vary with vintage, growing season precipitation, and fruit maturity metrics. Further, the correlation between fungal community dissimilarities and geographic distance suggests dispersal limitation and the vineyard as a source for abundant fungal taxa. Contrasting this observation, the lack of correlation between bacterial community dissimilarity and geographic distance suggests that environmental filtering is shaping these communities.

Successive orchard plantings of almond and other Prunus species exhibit reduced growth and yield in many California soils. This phenomenon, known as Prunus replant disease (PRD), can be prevented by preplant soil fumigation or anaerobic soil disinfestation, but its etiology is poorly understood and its incidence and severity are hard to predict. We report here on relationships among physicochemical variables, microbial community structure, and PRD induction in 25 diverse replant soils from California. In a greenhouse bioassay, soil was considered to be “PRD-inducing” when growth of peach seedlings in it was significantly increased by preplant fumigation and pasteurization, compared to an untreated control. PRD was induced in 18 of the 25 soils, and PRD severity correlated positively with soil exchangeable-K, pH, %clay, total %N, and electrical conductivity. The structure of bacterial, fungal, and oomycete communities differed significantly between the PRD-inducing and non-inducing soils, based on PERMANOVA of Bray Curtis dissimilarities. Bacterial class MB-A2-108 of phylum Actinobacteria had high relative abundances among PRD-inducing soils, while Bacteroidia were relatively abundant among non-inducing soils. Among fungi, many ASVs classified only to kingdom level were relatively abundant among PRD-inducing soils whereas ASVs of Trichoderma were relatively abundant among non-inducing soils. Random forest classification effectively discriminated between PRD-inducing and non-inducing soils, revealing many bacterial ASVs with high explanatory values. Random forest regression effectively accounted for PRD severity, with soil exchangeable-K and pH having high predictive value. Our work revealed several biotic and abiotic variables worthy of further examination in PRD etiology.

In this paper, we address the question of possible conceptual ways of thinking about organizations in the making. We begin by introducing the concept of border, which seems heuristic to us, to define organizational development as crossing borders. We then propose to consider the border crossing from an intrinsic point of view by adopting a transitional perspective. To address these transitional phenomena, we articulate two conceptual ergonomics frameworks: the course of action and the instrumental approach. Through two contrasting researches from the point of view of the fields of activity (travel narratives and a process of treating a customer demand in the energy field), we confront the ways to hybridize these two theoretical frameworks conceptually, methodologically and empirically. We highlight what results from this hybridization: the so-called transitional instruments that confer continuity to different scales. Finally, we discuss the perspectives opened by a transitional approach to think about organizational genesis.

In this paper, we propose to address the question of possible conceptual ways of thinking about organizations in the making. We begin by introducing the concept of boundary, which we feel to be heuristic when defining development as a crossing of borders. We then propose to consider boundary crossing from an intrinsic point of view by adopting a transitional prism. To address these transitional phenomena, we articulate two conceptual frameworks of ergonomics: course of action and the instrumental approach. Through two works of research that differ in terms of fields of activity (narrations of travel and a process for dealing with customer requests in the field of energy), we compare ways of conceptually, methodologically and empirically hybridizing these two theoretical frameworks. We highlight what results from this hybridization: transitional instruments that channel continuity on different scales. Finally, we discuss the perspectives that a transitional approach offers to think about organizational genesis.

In this paper, we propose to address the question of possible conceptual ways of thinking about organizations in the making. We begin by introducing the concept of borders, which seems heuristic to us, to define development as crossing borders. We then propose to consider the crossing boundary from an intrinsic point of view by adopting a transitional prism. To adress these transitional phenomena, we articulate two conceptual frameworks of ergonomics: the course of action and the instrumental approach. Through two contrasting researches from the point of view of the fields of activity (narrations of travel and a process of treatment of the customer demand in the field of energy), we confront the ways to hybridize these two theoretical frameworks conceptually, methodologically and empirically. We highlight what results from this hybridization: some transitional instruments that carry continuity on different scales. Finally, we discuss the perspectives opened by a transitional approach to thinking about organizational genesis.

Several universal genomic traits affect trade-offs in the capacity, cost, and efficiency of the biochemical information processing that underpins metabolism and reproduction. We analyzed the role of these traits in mediating the responses of a planktonic microbial community to nutrient enrichment in an oligotrophic, phosphorus-deficient pond in Cuatro Ciénegas, Mexico. This is one of the first whole-ecosystem experiments to involve replicated metagenomic assessment. Mean bacterial genome size, GC content, total number of tRNA genes, total number of rRNA genes, and codon usage bias in ribosomal protein sequences were all higher in the fertilized treatment, as predicted on the basis of the assumption that oligotrophy favors lower information-processing costs whereas copiotrophy favors higher processing rates. Contrasting changes in trait variances also suggested differences between traits in mediating assembly under copiotrophic versus oligotrophic conditions. Trade-offs in information-processing traits are apparently sufficiently pronounced to play a role in community assembly because the major components of metabolism—information, energy, and nutrient requirements—are fine-tuned to an organism’s growth and trophic strategy.

Recent explosive volcanic eruptions recorded worldwide (e.g. Hekla in 2000, Eyjafjallajökull in 2010, Cordón-Caulle in 2011) demonstrated the necessity for a better assessment of the eruption source parameters (ESPs; e.g. column height, mass eruption rate, eruption duration, and total grain-size distribution – TGSD) to reduce the uncertainties associated with the far-travelling airborne ash mass. Volcanological studies started to integrate observations to use more realistic numerical inputs, crucial for taking robust volcanic risk mitigation actions. On 23 November 2013, Etna (Italy) erupted, producing a 10 km height plume, from which two volcanic clouds were observed at different altitudes from satellites (SEVIRI, MODIS). One was retrieved as mainly composed of very fine ash (i.e. PM20), and the second one as made of ice/SO2 droplets (i.e. not measurable in terms of ash mass). An atypical north-easterly wind direction transported the tephra from Etna towards the Calabria and Apulia regions (southern Italy), permitting tephra sampling in proximal (i.e. ∼ 5–25 km from the source) and medial areas (i.e. the Calabria region, ∼ 160 km). A primary TGSD was derived from the field measurement analysis, but the paucity of data (especially related to the fine ash fraction) prevented it from being entirely representative of the initial magma fragmentation. To better constrain the TGSD assessment, we also estimated the distribution from the X-band weather radar data. We integrated the field and radar-derived TGSDs by inverting the relative weighting averages to best fit the tephra loading measurements. The resulting TGSD is used as input for the FALL3D tephra dispersal model to reconstruct the whole tephra loading. Furthermore, we empirically modified the integrated TGSD by enriching the PM20 classes until the numerical results were able to reproduce the airborne ash mass retrieved from satellite data. The resulting TGSD is inverted by best-fitting the field, ground-based, and satellite-based measurements. The results indicate a total erupted mass of 1.2 × 109 kg, being similar to the field-derived value of 1.3 × 109 kg, and an initial PM20 fraction between 3.6 and 9.0 wt %, constituting the tail of the TGSD.

Abstract Numerical modeling of ash plume dispersal is an important tool for forecasting and mitigating potential hazards from volcanic ash erupted during explosive volcanism. Recent tephra dispersal models have been expanded to account for dynamic ash aggregation processes. However, there are very few studies on rates of disaggregation during transport. It follows that current models regard ash aggregation as irrevocable and may therefore overestimate aggregation-enhanced sedimentation. In this experimental study, we use industrial granulation techniques to artificially produce aggregates. We subject these to impact tests and evaluate their resistance to break-up processes. We find a dependence of aggregate stability on primary particle size distribution and solid particle binder concentration. We posit that our findings could be combined with eruption source parameters and implemented in future tephra dispersal models.

Oilseed rape (Brassica napus L.) is an oleoproteaginous crop characterized by low N use efficiency (NUE) that is mainly related to a weak Nitrogen Remobilization Efficiency (NRE) during the sequential leaf senescence of the vegetative stages. Based on the hypothesis that proteolysis efficiency is crucial for the improvement of leafNRE, our objective was to characterize key senescence-associated proteolytic mechanisms of two genotypes (Ténor and Samouraï) previously identified with contrasting NREs. To reach this goal, biochemical changes, protease activities and phytohormone patterns were studied in mature leaves undergoing senescence in two genotypes with contrasting NRE cultivated in a greenhouse under limiting or ample nitrate supply. The genotype with the higher NRE (Ténor) possessed enhanced senescence processes in response to nitrate limitation, and this led to greater degradation of soluble proteins compared to the other genotype (Samouraï). This efficient proteolysis is associated with (i) an increase in serine and cysteine protease (CP) activities and (ii) the appearance of new CP activities (RD21-like, SAG12-like, RD19-like, cathepsin-B, XBCP3-like and aleurain-like proteases) during senescence induced by N limitation. Compared to Samouraï, Ténor has a higher hormonal ratio ([salicylic acid] + [abscisic acid])/([cytokinins]) that promotes senescence, particularly under low N conditions, and this is correlated with the stronger protein degradation and serine/CP activities observed during senescence. Short statement: The improvement in N recycling during leaf senescence in a genotype of Brassica napus L. characterized by a high nitrogen remobilization efficiency is related to a high phytohormonal ratio ([salicylic acid] + [abscisic acid])/([cytokinins]) that promotes leaf senescence and is correlated with an increase or the induction of specific serine and cysteine protease activities.

Anaerobic soil disinfestation (ASD) is an organic amendment-based management practice for controlling soil-borne plant pathogens. Pathogen suppression appears to be carbon source-dependent and mediated by bacteria that proliferate and produce volatile organic compounds, as well as physico-chemical changes (i.e., elevated temperature, lowered redox potential and pH, release of metal ions) in soil. ASD is under study for adoption in tree crops as a replacement for chemical-fumigation, but its widespread use is limited by incomplete understanding of its suppression mechanisms and high economic costs. The carbon substrate is one component of the ASD process that can be optimized to enhance effectiveness and affordability. While rice bran is currently the standard carbon source used for ASD, we identified three alternative substrates (molasses, mustard seed meal, and tomato pomace) that are similar in efficacy to rice bran at generating and sustaining soil anoxia and reducing populations of introduced plant pathogens. Here, we used replicated ASD field trials to determine if rice bran and the alternative carbon substrates would elicit similar soil bacterial communities (characterized via amplicon sequencing of the 16S rRNA gene v4 region) and to assess if any observed community shifts were consistent across repeated trials. We found significant, but minimal differences in community composition between ASD carbon treatments (F4, 30 = 2.80, P < 0.001, R2 = 0.22) and trials (F1, 30 = 5.24, P < 0.001, R2 = 0.10). In both trials, the abundances of Bacteroidales, Clostridiales, Selenomonadales, and Enterobacteriales increased significantly (>5 log2 fold change) in all ASD treatments compared to untreated controls. A group of shared core genera belonging to the Clostridiales and Selenomonadales were identified in both trials and constituted 22.6 and 21.5% of the communities. Bacterial taxa that were most responsive to ASD treatments had the genomic potential for denitrification, nitrogen fixation, and fermentation reactions that produce organic acids (such as acetate and butyrate) known to inhibit in vitro growth of plant pathogens based on predicted metagenomes. Together, these results indicate that reproducible and effective implementation of ASD is achievable with alternative carbon substrates to rice bran.

Overexpression of G protein-coupled receptors (GPCRs) in tumours is widely used to develop GPCR-targeting radioligands for solid tumour imaging in the context of diagnosis and even treatment. The human vasoactive neuropeptide urotensin II (hUII), which shares structural analogies with somatostatin, interacts with a single high affinity GPCR named UT. High expression of UT has been reported in several types of human solid tumours from lung, gut, prostate, or breast, suggesting that UT is a valuable novel target to design radiolabelled hUII analogues for cancer diagnosis. In this study, two original urotensinergic analogues were first conjugated to a DOTA chelator via an aminohexanoic acid (Ahx) hydrocarbon linker and then -hUII and DOTA-urantide, complexed to the radioactive metal indium isotope to successfully lead to radiolabelled DOTA-Ahx-hUII and DOTA-Ahx-urantide. The 111In-DOTA-hUII in human plasma revealed that only 30% of the radioligand was degraded after a 3-h period. DOTA-hUII and DOTA-urantide exhibited similar binding affinities as native peptides and relayed calcium mobilization in HEK293 cells expressing recombinant human UT. DOTA-hUII, not DOTA-urantide, was able to promote UT internalization in UT-expressing HEK293 cells, thus indicating that radiolabelled 111In-DOTA-hUII would allow sufficient retention of radioactivity within tumour cells or radiolabelled DOTA-urantide may lead to a persistent binding on UT at the plasma membrane. The potential of these radioligands as candidates to target UT was investigated in adenocarcinoma. We showed that hUII stimulated the migration and proliferation of both human lung A549 and colorectal DLD-1 adenocarcinoma cell lines endogenously expressing UT. In vivo intravenous injection of 111In-DOTA-hUII in C57BL/6 mice revealed modest organ signals, with important retention in kidney. 111In-DOTA-hUII or 111In-DOTA-urantide were also injected in nude mice bearing heterotopic xenografts of lung A549 cells or colorectal DLD-1 cells both expressing UT. The observed significant renal uptake and low tumour/muscle ratio (around 2.5) suggest fast tracer clearance from the organism. Together, DOTA-hUII and DOTA-urantide were successfully radiolabelled with 111Indium, the first one functioning as a UT agonist and the second one as a UT-biased ligand/antagonist. To allow tumour-specific targeting and prolong body distribution in preclinical models bearing some solid tumours, these radiolabelled urotensinergic analogues should be optimized for being used as potential molecular tools for diagnosis imaging or even treatment tools.

This article presents the genesis and implementation of a method that consisted in simulating the activity of processing a customer request in the field of the service relationship. The purpose of this simulation was twofold: to reveal a collective activity that unfolds in a distributed way in time and space and to identify the levers of transformation to facilitate the service relationship and make it more fluid. This simulation, known as "Transverse Reflexive Simulation", elicits the work thanks to the knowledge acquired on human activity in its various dimensions in an existing research programme in the R&D (Research and Development) division of a large company. It makes it possible to work on continuity, an element crucial to quality of service and customer satisfaction, by opening spaces for constructing this continuity. By promoting the development of individuals, collectives and organizations, Transverse Reflexive Simulation contributes to the company's long-term performance.

This article presents the genesis and implementation of a method that consisted in simulating the activity of processing a customer request in the field of the service relationship. The purpose of this simulation was twofold: to reveal a collective activity that unfolds in a distributed manner in time and space and to identify the levers of transformation to facilitate and to make the service relationship more fluid. This simulation, known as “Transverse Reflexive Simulation”, elicits the work through the knowledge acquired on human activity in its various dimensions in a large company’s existing R&D (Research and Development) program. It allows one to work on continuity - element crucial to quality of service and customer satisfaction - by opening spaces in which to construct this continuity. By promoting the development of individuals, collectives and organizations, Transverse Reflexive Simulation contributes to a company’s long-term performance.

In a previous article, an algorithm for identifying therapeutic targets in Boolean networks modelling pathological mechanisms was introduced. In the present article, the improvements made on this algorithm, named kali, are described. These improvements are (i) the possibility to work on asynchronous Boolean networks, (ii) a finer assessment of therapeutic targets and (iii) the possibility to use multivalued logic. kali assumes that the attractors of a dynamical system, such as a Boolean network, are associated with the phenotypes of the modelled biological system. Given a logic-based model of pathological mechanisms, kali searches for therapeutic targets able to reduce the reachability of the attractors associated with pathological phenotypes, thus reducing their likeliness. kali is illustrated on an example network and used on a biological case study. The case study is a published logic-based model of bladder tumorigenesis from which kali returns consistent results. However, like any computational tool, kali can predict but cannot replace human expertise: it is a supporting tool for coping with the complexity of biological systems in the field of drug discovery.

The Blue Mussel (Mytilus edulis, L. 1758) is an ecologically important and commercially relevant bivalve. Because of its ability to bioconcentrate xenobiotics, it is also a widespread sentinel species for environmental pollution, which has been used in ecotoxicological studies for biomarker assessment. Consequently, numerous proteomics studies have been carried out in various research contexts using mussels of the genus Mytilus, which intended to improve our understanding of complex physiological processes related to reproduction, adaptation to physical stressors or shell formation and for biomarker discovery. Differential-display 2-DE proteomics relies on an extensive knowledge of the proteome with as many proteoforms identified as possible. To this end, extensive characterization of proteins was performed in order to increase our knowledge of the Mytilus gill proteome. On average, 700 spots were detected on 2-DE gels by colloidal blue staining, of which 122 different, non-redundant proteins comprising 203 proteoforms could be identified by tandem mass spectrometry. These proteins could be attributed to four major categories: (i) “metabolism”, including antioxidant defence and degradation of xenobiotics; (ii) “genetic information processing”, comprising transcription and translation as well as folding, sorting, repair and degradation; (iii) “cellular processes”, such as cell motility, transport and catabolism; (iv) “environmental information processing”, including signal transduction and signalling molecules and interaction. The role of cytoskeleton proteins, energetic metabolism, chaperones/stress proteins, protein trafficking and the proteasome are discussed in the light of the exigencies of the intertidal environment, leading to an enhanced stress response, as well as the structural and physiological particularities of the bivalve gill tissue.

Nutrient availability and ratios can play an important role in shaping microbial communities of freshwater ecosystems. The Cuatro Ciénegas Basin (CCB) in Mexico is a desert oasis where, perhaps paradoxically, high microbial diversity coincides with extreme oligotrophy. To better understand the effects of nutrients on microbial communities in CCB, a mesocosm experiment was implemented in a stoichiometrically imbalanced pond, Lagunita, which has an average TN:TP ratio of 122 (atomic). The experiment had four treatments, each with five spatial replicates – unamended controls and three fertilization treatments with different nitrogen:phosphorus (N:P) regimes (P only, N:P = 16 and N:P = 75 by atoms). In the water column, quantitative PCR of the 16S rRNA gene indicated that P enrichment alone favored proliferation of bacterial taxa with high rRNA gene copy number, consistent with a previously hypothesized but untested connection between rRNA gene copy number and P requirement. Bacterial and microbial eukaryotic community structure was investigated by pyrosequencing of 16S and 18S rRNA genes from the planktonic and surficial sediment samples. Nutrient enrichment shifted the composition of the planktonic community in a treatment-specific manner and promoted the growth of previously rare bacterial taxa at the expense of the more abundant, potentially endemic, taxa. The eukaryotic community was highly enriched with phototrophic populations in the fertilized treatment. The sediment microbial community exhibited high beta diversity among replicates within treatments, which obscured any changes due to fertilization. Overall, these results showed that nutrient stoichiometry can be an important factor in shaping microbial community structure.

In a context of changes to the economic environment and structural changes in companies which must now consider their performance in terms of their cross-functional processes, it is essential to understand the grounds of an organization’s efficiency when coping with its customers’ demands. One of these grounds is a cross-functional cooperation between actors involved in the same process, within the framework of a new kind of collective activity: cross-functional and transactional collective activity (Motté & Haradji, 2010 ; Poret, 2015). This collective activity requires actors who are involved in the same process to cooperate by crossing the organization’s boundaries. From an understanding of the different methods of coordination which form the basis of cooperation between actors of the same cross-functional process, this research highlights the existence of instruments enabling said actors to cross the organization’s classic boundaries in order to cooperate (Cooperative Transitional Instruments (Poret, ibid)) and proposes a criterion for the design of IT and organizational systems in order to durably root transversality and implement the Power to Act Together at the heart of organizations.

With regard to transformations of the economic environment and structural changes in companies which now conceptualize their performance on the basis of their cross-functional processes, it is essential to understand the efficiency levers that organisations employ to cope with customer requests. One of these levers is cross-functional cooperation between actors who are members of the same process, based on a new kind of collective activity : cross-functional and transactional collective activity (Motté & Haradji, 2010 ; Poret, 2015). This collective activity involves actors who are members of a same process cooperating by crossing over the organisation’s various boundaries. Taking an understanding of the modes of coordination which form the basis for cooperation between members of the same cross-functional process, this research highlights the existence of instruments (Cooperative Transitional Instruments (Poret, ibid)) that allow these actors to cross the organisation’s typical boundaries in order to cooperate, and proposes a criteria for the IT and organisational system in order to durably anchor cross-functionality and enable the Power to Act Together at the heart of organisations.

Cystic duct carcinoma is known to have a better prognosis compared to its location in other biliary ducts. Only one case with a survival over ten years has been previously published. The authors report a case of survival over 13 years without recurrence or metastasis. Preoperative diagnosis of cystic duct tumor was carried in a 66-year-old male. Under the diagnosis of carcinoma of the cystic duct, the patient underwent en bloc resection of the gallbladder, cystic duct, hepaticocholedochus and lymph node dissection. A Roux-en-Y hepaticojejunostomy was performed. Histological examination revealed a moderately differentiated adenocarcinoma of the cystic duct. Five months later the patient underwent second look surgery for benign obstruction of the hepaticojejunal anastomosis. The patient is still doing well 13 years later without any local recurrence or metastasis. To our knowledge, this is the longest disease-free survival ever published in the literature. This case sustains that better and longer survival is possible with a real chance of potential cure if radical surgery is performed.