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Abstract Congenital erythropoietic porphyria (CEP), or Gunther disease, is a rare genetic disease responsible for severe dermatologic, hepatic and/or haematological damages related to the deficient activity of the uroporphyrinogen III synthase. Allogeneic stem cell transplantation (Allo‐SCT) represents the only curative treatment and few allotransplanted cases have been reported in children but not in adults. Here we report for the first time the successful cure of a 46‐year old man with CEP with a 5‐year follow‐up after Allo‐SCT.

ABSTRACTThe human T-lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus whose transmission relies primarily on cell-to-cell contacts as cell-free viruses are poorly infectious. Among the intercellular transmission routes described, HTLV-1 biofilms are adhesive structures polarized at the cell surface that confine virions in a protective environment, which is believed to promote their simultaneous delivery during infection. Here, we show that several tetraspanins are enriched in HTLV-1 biofilms and incorporated into the viral envelope. However, we report that only the tetraspanin CD82 interacts with HTLV-1 Gag proteins which initiates their polarization into viral biofilms. Also, we demonstrate that CD82 maintains HTLV-1 biofilm polarization and favors viral transmission, as its silencing induces a complete reorganization of viral clusters at the cell surface and reduces the ability of infected T-cells to transmit the virus. Our results highlight the crucial role of CD82 and its glycosylation state in the architectural organization of HTLV-1 biofilms and their subsequent transfer through intercellular contacts.IMPORTANCEIn the early stages of infection, human T-lymphotropic virus type 1 (HTLV-1) dissemination within its host is believed to rely mostly on cell-to-cell contacts. Past studies unveiled a novel mechanism of HTLV-1 intercellular transmission based on the remodeling of the host-cell extracellular matrix and the generation of cell-surface viral assemblies whose structure, composition, and function resemble bacterial biofilms. These polarized aggregates of infectious virions, identified as viral biofilms, allow the bulk delivery of viruses to target cells and may help to protect virions from immune attacks. However, viral biofilms’ molecular and functional description is still in its infancy, although it is crucial to fully decipher retrovirus pathogenesis. Here, we explore the function of cellular tetraspanins (CD9, CD81, CD82) that we detect inside HTLV-1 particles within biofilms. Our results demonstrate specific roles for CD82 in the cell-surface distribution and intercellular transmission of HTLV-1 biofilms, which we document as two essential parameters for efficient viral transmission. At last, our findings indicate that N-glycosylation of cell-surface molecules, including CD82, is required for the polarization of HTLV-1 biofilms and for the efficient transmission of HTLV-1 between T-lymphocytes.

ABSTRACT The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The capacity of HTLV-1 to infect central nervous system (CNS) resident cells, together with the neuroimmune-driven response, has not been well-established. Here, we combined the use of human induced pluripotent stem cells (hiPSC) and of naturally STLV-1-infected nonhuman primates (NHP) as models with which to investigate HTLV-1 neurotropism. Hence, neuronal cells obtained after hiPSC differentiation in neural polycultures were the main cell population infected by HTLV-1. Further, we report the infection of neurons with STLV-1 in spinal cord regions as well as in brain cortical and cerebellar sections of postmortem NHP. Additionally, reactive microglial cells were found in infected areas, suggesting an immune antiviral response. These results emphasize the need to develop new efficient models by which to understand HTLV-1 neuroinfection and suggest an alternative mechanism that leads to HAM/TSP.

There is increasing evidence that viral infections are the source/origin of various types of encephalitis, encephalomyelitis, and other neurological and cognitive disorders. While the involvement of certain viruses, such as the Nipah virus and measles virus, is known, the mechanisms of neural invasion and the factors that trigger intense immune reactions are not fully understood. Based on recent publications, this review discusses the role of the immune response, interactions between viruses and glial cells, and cytokine mediators in the development of inflammatory diseases in the central nervous system. It also highlights the significant gaps in knowledge regarding these mechanisms.

The effect of back-end of line (BEOL) process on cell performance and reliability of Phase-Change Memory embedded in a 28nm FD-SOI platform (ePCM) is discussed. The microscopic evolution of the Ge-rich GST alloy during process is the focus of the first part of the paper. A new metric for quantification of active material modifications is introduced to better follow its evolution with process sequence. Ge clustering has been shown to occur during the fabrication, impacting the pristine resistance and the after forming cell performance. Two different BEOL processes are then benchmarked in terms of key performance. An optimized process is identified, and an extensive electrical characterization of array performance and reliability is done on the full 16MB chip. The optimized BEOL process results in a memory cell fully compatible with the requirements for demanding automotive applications.

Abstract Background The Human T-cell Lymphotropic Virus Type-1 (HTLV-1) is a blood-borne pathogen and etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 has currently infected up to 10 million globally with highly endemic areas in Japan, Africa, the Caribbean and South America. We have previously shown that Extracellular Vesicles (EVs) enhance HTLV-1 transmission by promoting cell–cell contact. Results Here, we separated EVs into subpopulations using differential ultracentrifugation (DUC) at speeds of 2 k (2000×g), 10 k (10,000×g), and 100 k (100,000×g) from infected cell supernatants. Proteomic analysis revealed that EVs contain the highest viral/host protein abundance in the 2 k subpopulation (2 k > 10 k > 100 k). The 2 k and 10 k populations contained viral proteins (i.e., p19 and Tax), and autophagy proteins (i.e., LC3 and p62) suggesting presence of autophagosomes as well as core histones. Interestingly, the use of 2 k EVs in an angiogenesis assay (mesenchymal stem cells + endothelial cells) caused deterioration of vascular-like-tubules. Cells commonly associated with the neurovascular unit (i.e., astrocytes, neurons, and macrophages) in the blood–brain barrier (BBB) showed that HTLV-1 EVs may induce expression of cytokines involved in migration (i.e., IL-8; 100 k > 2 k > 10 k) from astrocytes and monocyte-derived macrophages (i.e., IL-8; 2 k > 10 k). Finally, we found that EVs were able to promote cell–cell contact and viral transmission in monocytic cell-derived dendritic cell. The EVs from both 2 k and 10 k increased HTLV-1 spread in a humanized mouse model, as evidenced by an increase in proviral DNA and RNA in the Blood, Lymph Node, and Spleen. Conclusions Altogether, these data suggest that various EV subpopulations induce cytokine expression, tissue damage, and viral spread.

Abstract Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As HTLV-1, STLV-1 is the etiological agent of ATL, while no case of TSP/HAM has been described. Given its similarities with HTLV-1, STLV-1 represents a unique tool used for performing clinical studies, vaccine studies as well as basic science.

Abstract Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and the demyelinating neuroinflammatory disease known as HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), was the first human retrovirus to be discovered. T-cells, which represent the main reservoir for HTLV-1, have been the main focus of studies aimed at understanding viral transmission and disease progression. However, other cell types such as myeloid cells are also target of HTLV-1 infection and display functional alterations as a consequence. In this work, we review the current investigations that shed light on infection, transmission and functional alterations subsequent to HTLV-1 infection of the different myeloid cells types, and we highlight the lack of knowledge in this regard.

The oleanolic acid (1), a natural pentacyclic triterpenoid, was quantitatively isolated from pomace olive (Olea europaea L.) under ultra-sonication conditions (6.8 g (3.4 mg/g DW)). Two series of oleanolic acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethylester 6a–g and new oleanolic acid-1-phenyl-1H-[1,2,3]triazol-5-ylmethylester 7a–g congeners have been designed and synthesized in an attempt to develop potent anticancer and anti-inflammatory agents. A facile and regiospecific synthesis of 1,2,3-triazoles catalyzed by Cu(I) (CuAAC) or Ru(II) (RuAAC) and conducted under microwave conditions of oleanolic acid–alkyne derivative 5 with various aromatic azides 2a–g afforded a series of 1,4- and 1,5-triazolyl derivatives, respectively. Their structures were confirmed by using 1H NMR, 13C NMR, NOESY and HRMS analysis. Most of the compounds were evaluated for their anticancer and anti-inflammatory activities. Oleanolic acid 1 exhibited promising anticancer activity against murine breast (EMT-6) and human colon (SW480) cancer cells. Its derivatives 6b and 6c (1,4-regioisomers) and 7b (1,5-regioisomer) were found to be anti-cancer agents. On the other hand, only 6b displays anti-inflammatory activity. Keywords: Oleanolic acid, Triazoles, Click-chemistry, Microwave, Anticancer activity, Anti-inflammatory activity

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cells from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFNα+ DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1α and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFNγ responsiveness of NK cells, suggesting an increased sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.

S’installant et colonisant des biotopes très divers, bordures de rivières et d’infrastructures linéaires, friches, etc., les renouées asiatiques peuvent concerner de nombreux gestionnaires publics et propriétaires privés. Or, trouver des moyens efficaces pour contrôler leur développement relèvent encore aujourd’hui du défi. Cependant, comme l’illustre cet article, en deux décennies, les compétences et l’expertise sur le terrain progressent ainsi que les échanges entre la recherche et la gestion, l’ensemble contribuant à faire évoluer les réflexions et les pratiques.

Introduites en France à la fin du dix-neuvième siècle, les renouées asiatiques sont classées au niveau mondial parmi les espèces exotiques envahissantes les plus menaçantes pour la biodiversité. Dans cet article, écologues, géographes, historiens et gestionnaires font le point des éléments de connaissances sur ces espèces, objets de nombreux travaux de recherches et d’essais de gestion en France, en Europe et dans le monde.

Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T cell leukemia/lymphoma (ATLL) and of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), was identified a few years before Human Immunodeficiency Virus (HIV). However, forty years later, our comprehension of HTLV-1 immune detection and the host immune responses to HTLV-1 is far more limited than for HIV. In addition to innate and adaptive immune responses that rely on specialized cells of the immune system, host cells may also express a range of antiviral factors that inhibit viral replication at different stages of the cycle, in a cell-autonomous manner. Multiple antiviral factors allowing such an intrinsic immunity have been primarily and extensively described in the context HIV infection. Here, we provide an overview of whether known HIV restriction factors might act on HTLV-1 replication. Interestingly, many of them do not exert any antiviral activity against HTLV-1, and we discuss viral replication cycle specificities that could account for these differences. Finally, we highlight future research directions that could help to identify antiviral factors specific to HTLV-1.

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To date, it is the unique published example of a virus able to form a biofilm at the surface of infected cells. Deeply studied in bacteria, bacterial biofilms represent multicellular assemblies of bacteria in contact with a surface and shielded by the extracellular matrix (ECM). Microbial lifestyle in biofilms, either viral or bacterial, is opposed structurally and physiologically to an isolated lifestyle, in which viruses or bacteria freely float in their environment. HTLV-1 biofilm formation is believed to be promoted by viral proteins, mainly Tax, through remodeling of the ECM of the infected cells. HTLV-1 biofilm has been linked to cell-to-cell transmission of the virus. However, in comparison to bacterial biofilms, very little is known on kinetics of viral biofilm formation or dissemination, but also on its pathophysiological roles, such as escape from immune detection or therapeutic strategies, as well as promotion of leukemogenesis. The switch between production of cell-free isolated virions and cell-associated viral biofilm, although not fully apprehended yet, remains a key step to understand HTLV-1 infection and pathogenesis.

Selection of sugar beet (Beta vulgaris L.) cultivars that are resistant to Cercospora Leaf Spot (CLS) disease is critical to increase yield. Such selection requires an automatic, fast, and objective method to assess CLS severity on thousands of cultivars in the field. For this purpose, we compare the use of submillimeter scale RGB imagery acquired from an Unmanned Ground Vehicle (UGV) under active illumination and centimeter scale multispectral imagery acquired from an Unmanned Aerial Vehicle (UAV) under passive illumination. Several variables are extracted from the images (spot density and spot size for UGV, green fraction for UGV and UAV) and related to visual scores assessed by an expert. Results show that spot density and green fraction are critical variables to assess low and high CLS severities, respectively, which emphasizes the importance of having submillimeter images to early detect CLS in field conditions. Genotype sensitivity to CLS can then be accurately retrieved based on time integrals of UGV- and UAV-derived scores. While UGV shows the best estimation performance, UAV can show accurate estimates of cultivar sensitivity if the data are properly acquired. Advantages and limitations of UGV, UAV, and visual scoring methods are finally discussed in the perspective of high-throughput phenotyping.

Research on brain–computer interfaces (BCIs) has become more democratic in recent decades, and experiments using electroencephalography (EEG)-based BCIs has dramatically increased. The variety of protocol designs and the growing interest in physiological computing require parallel improvements in processing and classification of both EEG signals and bio signals, such as electrodermal activity (EDA), heart rate (HR) or breathing. If some EEG-based analysis tools are already available for online BCIs with a number of online BCI platforms (e.g., BCI2000 or OpenViBE), it remains crucial to perform offline analyses in order to design, select, tune, validate and test algorithms before using them online. Moreover, studying and comparing those algorithms usually requires expertise in programming, signal processing and machine learning, whereas numerous BCI researchers come from other backgrounds with limited or no training in such skills. Finally, existing BCI toolboxes are focused on EEG and other brain signals but usually do not include processing tools for other bio signals. Therefore, in this paper, we describe BioPyC, a free, open-source and easy-to-use Python platform for offline EEG and biosignal processing and classification. Based on an intuitive and well-guided graphical interface, four main modules allow the user to follow the standard steps of the BCI process without any programming skills: (1) reading different neurophysiological signal data formats, (2) filtering and representing EEG and bio signals, (3) classifying them, and (4) visualizing and performing statistical tests on the results. We illustrate BioPyC use on four studies, namely classifying mental tasks, the cognitive workload, emotions and attention states from EEG signals.

Plants harbor diverse microbial communities that colonize both below-ground and above-ground organs. Some bacterial members of these rhizosphere and phyllosphere microbial communities have been shown to contribute to plant defenses against pathogens. In this study, we characterize the pathogen-inhibiting potential of 78 bacterial isolates retrieved from endophytic and epiphytic communities living in the leaves of three grapevine cultivars. We selected two economically relevant pathogens, the fungus Botrytis cinerea causing gray mold and the oomycete Phytophthora infestans, which we used as a surrogate for Plasmopara viticola causing downy mildew. Our results showed that epiphytic isolates were phylogenetically more diverse than endophytic isolates, the latter mostly consisting of Bacillus and Staphylococcus strains, but that mycelial inhibition of both pathogens through bacterial diffusible metabolites was more widespread among endophytes than among epiphytes. Six closely related Bacillus strains induced strong inhibition (>60%) of Botrytis cinerea mycelial growth. Among these, five led to significant perturbation in spore germination, ranging from full inhibition to reduction in germination rate and germ tube length. Different types of spore developmental anomalies were observed for different strains, suggesting multiple active compounds with different modes of action on this pathogen. Compared with B. cinerea, the oomycete P. infestans was inhibited in its mycelial growth by a higher number and more diverse group of isolates, including many Bacillus but also Variovorax, Pantoea, Staphylococcus, Herbaspirillum, or Sphingomonas strains. Beyond mycelial growth, both zoospore and sporangia germination were strongly perturbed upon exposure to cells or cell-free filtrates of selected isolates. Moreover, three strains (all epiphytes) inhibited the pathogen’s growth via the emission of volatile compounds. The comparison of the volatile profiles of two of these active strains with those of two phylogenetically closely related, inactive strains led to the identification of molecules possibly involved in the observed volatile-mediated pathogen growth inhibition, including trimethylpyrazine, dihydrochalcone, and L-dihydroxanthurenic acid. This work demonstrates that grapevine leaves are a rich source of bacterial antagonists with strong inhibition potential against two pathogens of high economical relevance. It further suggests that combining diffusible metabolite-secreting endophytes with volatile-emitting epiphytes might be a promising multi-layer strategy for biological control of above-ground pathogens.

Human T-cell leukemia virus-1 (HTLV-1) is a neglected and incurable retrovirus estimated to infect 5 to 10 million worldwide. Specific indigenous Australian populations report infection rates of more than 40%, suggesting a potential evolution of the virus with global implications. HTLV-1 causes adult T-cell leukemia/lymphoma (ATLL), and a neurological disease named HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Even though HTLV-1 transmission primarily occurs from cell-to-cell, there is still a gap of knowledge regarding the mechanisms of viral spread and disease progression. We have recently shown that Extracellular Vesicles (EVs) ubiquitously produced by cells may be used by HTLV-1 to transport viral proteins and RNA, and elicit adverse effects on recipient uninfected cells. The viral proteins Tax and HBZ are involved in disease progression and impairment of autophagy in infected cells. Here, we show that activation of HTLV-1 via ionizing radiation (IR) causes a significant increase of intracellular Tax, but not EV-associated Tax. Also, lower density EVs from HTLV-1-infected cells, separated by an Iodixanol density gradient, are positive for gp61+++/Tax+++/HBZ+ proteins (HTLV-1 EVs). We found that HTLV-1 EVs are not infectious when tested in multiple cell lines. However, these EVs promote cell-to-cell contact of uninfected cells, a phenotype which was enhanced with IR, potentially promoting viral spread. We treated humanized NOG mice with HTLV-1 EVs prior to infection and observed an increase in viral RNA synthesis in mice compared to control (EVs from uninfected cells). Proviral DNA levels were also quantified in blood, lung, spleen, liver, and brain post-treatment with HTLV-1 EVs, and we observed a consistent increase in viral DNA levels across all tissues, especially the brain. Finally, we show direct implications of EVs in viral spread and disease progression and suggest a two-step model of infection including the release of EVs from donor cells and recruitment of recipient cells as well as an increase in recipient cell-to-cell contact promoting viral spread.

The dynamics of the Green Leaf Area Index (GLAI) is of great interest for numerous applications such as yield prediction and plant breeding. We present a high-throughput model-assisted method for characterizing GLAI dynamics in maize (Zea mays subsp. mays) using multispectral imagery acquired from an Unmanned Aerial Vehicle (UAV). Two trials were conducted with a high diversity panel of 400 lines under well-watered and water-deficient treatments in 2016 and 2017. For each UAV flight, we first derived GLAI estimates from empirical relationships between the multispectral reflectance and ground level measurements of GLAI achieved over a small sample of microplots. We then fitted a simple but physiologically sound GLAI dynamics model over the GLAI values estimated previously. Results show that GLAI dynamics was estimated accurately throughout the cycle (R2 > 0.9). Two parameters of the model, biggest leaf area and leaf longevity, were also estimated successfully. We showed that GLAI dynamics and the parameters of the fitted model are highly heritable (0.65 ≤ H2 ≤ 0.98), responsive to environmental conditions, and linked to yield and drought tolerance. This method, combining growth modeling, UAV imagery and simple non-destructive field measurements, provides new high-throughput tools for understanding the adaptation of GLAI dynamics and its interaction with the environment. GLAI dynamics is also a promising trait for crop breeding, and paves the way for future genetic studies.

Les renouées asiatiques sont parmi les plantes invasives les plus largement répandues en métropole. Comme elles sont susceptibles de s'installer en fourrés monospécifiques éliminant toute strate herbacée ou arbustive dans des biotopes très divers, elles concernent donc de très nombreux gestionnaires publics et propriétaires privés. Au fil des années, les possibilités techniques de leur gestion ont bénéficié d'une très large diffusion d'informations permettant de les réguler dans diverses situations. Toutefois, de nombreux gestionnaires ont été confrontés à la nécessité d'interventions régulières devant être adaptées au contexte local de colonisation pour permettre un entretien à long terme des sites. Les acquis des recherches menées en parallèle sur ces espèces ont contribué à faire évoluer les représentations des enjeux et des démarches de cette gestion, passant progressivement d'une lutte plus ou moins systématique vers un "vivre avec" acceptant les limitations techniques et financières des interventions. Au fur et à mesure des gains de compétence qu'ils incorporent dans leurs démarches et leurs interventions, les gestionnaires participent de manière croissante à cet apprentissage collectif permanent qu'est en fait la gestion de ces espèces.

Introduites en France à la fin du dix-neuvième siècle, les renouées asiatiques sont classées au niveau mondial parmi les espèces exotiques envahissantes les plus menaçantes pour la biodiversité. Dans cet article, écologues, géographes, historiens et gestionnaires font le point des éléments de connaissances sur ces espèces, objets de nombreux travaux de recherches et d'essais de gestion en France, en Europe et dans le monde.

Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs. Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal β-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs. Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity.

Total above-ground biomass at harvest and ear density are two important traits that characterize wheat genotypes. Two experiments were carried out in two different sites where several genotypes were grown under contrasted irrigation and nitrogen treatments. A high spatial resolution RGB camera was used to capture the residual stems standing straight after the cutting by the combine machine during harvest. It provided a ground spatial resolution better than 0.2 mm. A Faster Regional Convolutional Neural Network (Faster-RCNN) deep-learning model was first trained to identify the stems cross section. Results showed that the identification provided precision and recall close to 95%. Further, the balance between precision and recall allowed getting accurate estimates of the stem density with a relative RMSE close to 7% and robustness across the two experimental sites. The estimated stem density was also compared with the ear density measured in the field with traditional methods. A very high correlation was found with almost no bias, indicating that the stem density could be a good proxy of the ear density. The heritability/repeatability evaluated over 16 genotypes in one of the two experiments was slightly higher (80%) than that of the ear density (78%). The diameter of each stem was computed from the profile of gray values in the extracts of the stem cross section. Results show that the stem diameters follow a gamma distribution over each microplot with an average diameter close to 2.0 mm. Finally, the biovolume computed as the product of the average stem diameter, the stem density, and plant height is closely related to the above-ground biomass at harvest with a relative RMSE of 6%. Possible limitations of the findings and future applications are finally discussed.

Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1). HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL), or a neurological disorder named Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). In vivo, HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells and dendritic cells. There is a strong correlation between HTLV-1 proviral load (PVL) and clinical status of infected individuals. Thus, reducing PVL could be part of a strategy to prevent or treat HTLV-1-associated diseases among carriers. Treatment of ATLL patients using conventional chemotherapy has very limited benefit. Some chronic and acute ATLL patients are, however, efficiently treated with a combination of interferon α and zidovudine (IFN-α/AZT), to which arsenic trioxide is added in some cases. On the other hand, no efficient treatment for TSP/HAM patients has been described yet. It is therefore crucial to develop therapies that could either prevent the occurrence of HTLV-1-associated diseases or at least block the evolution of the disease in the early stages. In vivo, reverse transcriptase (RT) activity is low in infected cells, which is correlated with a clonal mode of viral replication. This renders infected cells resistant to nucleoside RT inhibitors such as AZT. However, histone deacetylase inhibitors (HDACi) associated to AZT efficiently induces viral expression and prevent de novo cellular infection. In asymptomatic STLV-1 infected non-human primates, HDACi/AZT combination allows a strong decrease in the PVL. Unfortunately, rebound in the PVL occurs when the treatment is stopped, highlighting the need for better antiviral compounds. Here, we review previously used strategies targeting HTLV-1 replication. We also tested a series of HIV-1 RT inhibitors in an in vitro anti-HTLV-1 screen, and report that bis-POM-PMEA (adefovir dipivoxil) and bis-POC-PMPA (tenofovir disoproxil) are much more efficient compared to AZT to decrease HTLV-1 cell-to-cell transmission in vitro. Our results suggest that revisiting already established antiviral drugs is an interesting approach to discover new anti-HTLV-1 drugs.

Si les macrophytes sont souvent envisagés comme des nuisances, ils participent fortement aux fonctionnements écologiques des milieux aquatiques. De fait, il est primordial de les prendre en compte. Comment ont-ils été étudiés et analysés au cours des quatre dernières décennies ? Comment cette perception a-t-elle évolué et quelles relations unissent et opposent les macrophytes aux activités humaines qui les entourent ?

The capacity of LiDAR and Unmanned Aerial Vehicles (UAVs) to provide plant height estimates as a high-throughput plant phenotyping trait was explored. An experiment over wheat genotypes conducted under well watered and water stress modalities was conducted. Frequent LiDAR measurements were performed along the growth cycle using a phénomobile unmanned ground vehicle. UAV equipped with a high resolution RGB camera was flying the experiment several times to retrieve the digital surface model from structure from motion techniques. Both techniques provide a 3D dense point cloud from which the plant height can be estimated. Plant height first defined as the z-value for which 99.5% of the points of the dense cloud are below. This provides good consistency with manual measurements of plant height (RMSE = 3.5 cm) while minimizing the variability along each microplot. Results show that LiDAR and structure from motion plant height values are always consistent. However, a slight under-estimation is observed for structure from motion techniques, in relation with the coarser spatial resolution of UAV imagery and the limited penetration capacity of structure from motion as compared to LiDAR. Very high heritability values (H2> 0.90) were found for both techniques when lodging was not present. The dynamics of plant height shows that it carries pertinent information regarding the period and magnitude of the plant stress. Further, the date when the maximum plant height is reached was found to be very heritable (H2> 0.88) and a good proxy of the flowering stage. Finally, the capacity of plant height as a proxy for total above ground biomass and yield is discussed.

[This corrects the article DOI: 10.1371/journal.ppat.1006353.].

Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively. These different contacts may impact HTLV-1 ability to infect DCs and its subsequent transfer to T-cells. Using in vitro monocyte-derived IL-4 DCs, TGF-β DCs and IFN-α DCs that mimic DCs contacting HTLV-1 in vivo, we show here that despite their increased ability to capture HTLV-1 virions, IFN-α DCs restrict HTLV-1 productive infection. Surprisingly, we then demonstrate that it is not due to the antiviral activity of type-I interferon produced by IFN-α DCs, but that it is likely to be linked to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-α DCs. Finally, we demonstrate that, in contrast to IL-4 DCs, IFN-α DCs are impaired in their capacity to transfer HTLV-1 to CD4 T-cells, both after viral capture and trans-infection and after their productive infection. In conclusion, the nature of the DCs encountered by HTLV-1 upon primo-infection and the viral trafficking route through the vesicular pathway of these cells determine the efficiency of viral transmission to T-cells, which may condition the fate of infection.

La Trame verte et bleue permet aux espèces fragiles de supporter les modifications du paysage. Mais cette plus grande facilité de circulation est aussi offerte aux espèces invasives qui se développent avec la croissance des échanges mondiaux. Comment envisager ce problème et quels moyens mettre en œuvre pour y faire face ?

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.

Considérés tantôt comme des nuisances, tantôt comme des atouts, les macrophytes restent au cœur de nombreux débats. Quelle en est l’histoire récente ? Comment envisager l’avenir avec ces acteurs importants des milieux aquatiques ?

Afin d'élaborer des stratégies de gestion efficaces, il est nécessaire de mieux connaître les espèces exotiques envahissantes et de pouvoir les classer selon leur potentiel invasif. En France, le groupe de travail national sur les invasions biologiques en milieux aquatiques a engagé la mise en place d’une liste des espèces animales et végétales introduites en milieux aquatiques d'eau douce ou marins, afin de contribuer à dresser un premier bilan de la situation sur le territoire métropolitain.

Mener une politique de gestion efficace contre les phénomènes de prolifération des espèces exotiques envahissantes passe par des mesures de réglementation, mais aussi de prévention, nécessitant la mise en place de réseaux organisés de surveillance et de détection précoce de nouvelles espèces sur le territoire. Comment mieux organiser ces réseaux et coordonner l'action des différents acteurs, scientifiques, gestionnaires, associations et pouvoirs publics ? Quelques pistes nous sont suggérées dans cet article.It is quite difficult to eradicate an invasive alien species when it has already begun to spread. Even containment is very complicated, expensive andmay be harmful for natural ecosystems. For these reasons, it is necessary to improve prevention in order to foresee future invasions. The creation of a national list prioritized by negative impacts and specifying restrictivemeasures (black list) would be a consistent progress for the enhancement of actual legislation and the nation could take a step forward on the way to prevention. In the same way, voluntary approaches and participative initiatives can be developed as it is already done for several years with different stakeholders. Finally, because of the unfeasibility tomaster the knowledge of incoming species, setting up surveillance networks is essential. These networks are useful for a better detection of newly established species, but they alsomust facilitate rapid responses to control incipient populations of undesirable invaders. With the purpose of driving these networks to optimization, early detection areas have to be targeted and specific toolsmust be developed. This new strategy also involves a better targeting and training of the stakeholders that willmake it become alive.

Élaborer des stratégies d'action pour une meilleure gestion des invasions biologiques dans les écosystèmes aquatiques, proposer des outils opérationnels à destination des gestionnaires et des décideurs, mais aussi définir des enjeux scientifiques à long terme et contribuer à une expertise nationale, voire internationale dans le domaine : tels sont les objectifs et les missions du groupe de travail IBMA piloté par l'Onema et Irstea. En voici les premières réalisations.

Face aux enjeux environnementaux et économiques représentés par la présence d'espèces exotiques envahissantes dans les écosystèmes aquatiques continentaux, des actions sont déjà menées en France comme dans tout le reste du monde pour en améliorer la gestion. Prévention, détection précoce, rapidité d'intervention, apports des sciences humaines... quelles sont les marges de progrès et quelles sont les perspectives de réponse aux besoins des gestionnaires ?

Enjeu de recherche scientifique majeur, les espèces exotiques envahissantes représentent également des sources importantes de difficultés pour les populations humaines qui y sont confrontées, notamment pour les responsables des territoires envahis qui doivent décider et engager des actions pour les résoudre. Faut-il intervenir ? Quelles techniques utilisées pour se débarrasser des espèces invasives ou bien comment faire pour vivre avec ? Des questions abordées ici pour tenter d'améliorer la gestion de ces espèces.

Avec la multiplication des échanges internationaux, la prolifération des espèces envahissantes est devenue un problème mondial. Pour tenter d'y répondre efficacement, les instances nationales et européennes élaborent et mettent en œuvre des stratégies de prévention et de lutte contre ces espèces.

Data on aquatic fauna and flora have been collected for almost two centuries. More or less well conserved, these old data are used in setting up projects for biodiversity conservation and evaluation. To what purpose can the data be put? What precautions must be taken to ensure judicious use?

Water primrose, oxygen weed and Reynoutria are invasive species that have been monitored for years in the framework of biodiversity conservation and management policies. How effective have these policies been with respect to these invasive species?

Water primrose, oxygen weed and Reynoutria are invasive species that have been monitored for years in the framework of biodiversity conservation and management policies. How effective have these policies been with respect to these invasive species?Water primrose, oxygen weed and Reynoutria are invasive species that have been monitored for years in the framework of biodiversity conservation and management policies. How effective have these policies been with respect to these invasive species?

Data on aquatic fauna and flora have been collected for almost two centuries. More or less well conserved, these old data are used in setting up projects for biodiversity conservation and evaluation. To what purpose can the data be put? What precautions must be taken to ensure judicious use?

Jussies, lagarosiphons, renouées, tortues de Floride, ragondins... Ces espèces envahissantes font l'objet d'une surveillance depuis de nombreuses années dans le cadre de la politique de gestion et de conservation de la biodiversité. Quel bilan faire de ces politiques concernant ces espèces ?Water primrose, oxygen weed and Reynoutria are invasive species that have been monitored for years in the framework of biodiversity conservation and management policies. How effective have these policies been with respect to these invasive species?

Jussies, lagarosiphons, renouées, tortues de Floride, ragondins... Ces espèces envahissantes font l'objet d'une surveillance depuis de nombreuses années dans le cadre de la politique de gestion et de conservation de la biodiversité. Quel bilan faire de ces politiques concernant ces espèces ?

Depuis près de deux siècles, on recueille des données sur la faune et la flore aquatique. Ces données anciennes plus ou moins bien conservées sont utilisées pour construire des projets d'évaluation et de conservation de la biodiversité. Que peut-on en attendre ? Quelles précautions prendre pour une utilisation judicieuse ?

Depuis près de deux siècles, on recueille des données sur la faune et la flore aquatique. Ces données anciennes plus ou moins bien conservées sont utilisées pour construire des projets d'évaluation et de conservation de la biodiversité. Que peut-on en attendre ? Quelles précautions prendre pour une utilisation judicieuse ?Data on aquatic flora and fauna have been collected over the last two centuries, whilst human impacts on water and habitat quality have been increasing. Though the data have been used mainly by scientists in applied ecology, contemporary social concerns enhance their value for biodiversity issues and management. However, the appropriate use of historical data requires expert analysis of the various archives, taking into account the historical context and scientific aims at the time of collection. Review of historical data is essential for the conservation and efficient, sustainable management of biodiversity.