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1.
Mar Pollut Bull ; 202: 116419, 2024 May.
Article in English | MEDLINE | ID: mdl-38677107

ABSTRACT

Tracking PFAS in ecosystems is challenging. In this context, monitoring programs are crucial to fill data gaps, especially in marine environments, which are the ultimate outlets for these forever chemicals. The 2021 chemical contamination monitoring campaign along the French Mediterranean coast established a baseline for PFAS concentrations in mussels, with 90 % of measurements below quantification limits. When detected, long-chain PFCA's were predominant. Spatial distribution patterns suggested continuous PFAS inputs and complex dynamics, shaped by the influence of large watersheds and rivers (Rhône, Aude, Huveaune). Lapeyrade shallow lagoon stood out as the most contaminated site. Similar PFAS profiles in connected sites implied shared sources but raised questions about accumulation processes in mussels. While certain sites had evident sources (e.g., military airbase for Palo lagoon), others remained uncertain (e.g., Toulon bay). Coastal stations (Banyuls, Cap Agde, Brégançon, Pampelonne) showed PFAS contamination without clear onshore sources, possibly due to insufficient transportation process understanding.


Subject(s)
Biological Monitoring , Environmental Monitoring , Fluorocarbons , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Fluorocarbons/analysis , France , Animals , Mediterranean Sea , Bivalvia
2.
Sci Rep ; 14(1): 896, 2024 01 09.
Article in English | MEDLINE | ID: mdl-38195771

ABSTRACT

The dugong (Dugong dugon), a large marine mammal herbivore of the Indo-Pacific, is vulnerable to extinction at a global scale due to a combination of human-related threats including habitat degradation. The species forages on seagrass habitats (marine phanerogams) and plays a key role in the functioning and sensitivity of these declining coastal ecosystems. The trophic behaviour and plasticity of dugong populations in response to extrinsic and intrinsic factors are therefore crucial features to both dugong and seagrass conservation. Yet, this knowledge remains limited to few visual observations and analyses of mouth, stomach or faecal contents of stranded individuals. We take advantage of a long-term monitoring of stranded individuals from the endangered New Caledonian population to depict features of dugongs' trophic ecology from Carbon and Nitrogen stable isotopes. A total of 59 dugong skin samples were used to portrait the stable isotope niche of dugongs according to their sex and maturity. In light of previous work conducted in New Caledonia, a subset of these samples was used to model the trophic mix of dugong males and females. Our stable isotope mixing models used C and N isotope values of 10 taxa bbelonging to five divisions of metazoans, plants, and chromists. Our results represent the first estimate of the species dietary niche in the isotopic space. They suggest that the diet of dugong calves overlaps more with that of adult females (δ13C: - 6.38 ± 1.13 ‰; δ15N: 2.49 ± 1.10 ‰) than males (δ13C: - 5.92 ± 1.10 ‰; δ15N: 3.69 ± 1.28 ‰). Further, we highlight differences in the expected trophic mix of dugong adult males and females. From these, we formulate a sex-specific foraging behaviour hypothesis in dugongs, whereby lactating females could forage over smaller spatial ranges but more diverse food sources thanmales. The study emphasizes the importance of long-term stranding monitoring programs to study the ecology of marine mammals.. Finally, it depicts an ecological feature that may contribute to the sensitivity of vulnerable dugongs to ongoing changes on tropical coastal ecosystems.


Subject(s)
Caniformia , Dugong , Humans , Adult , Female , Male , Animals , Cattle , Ecosystem , Lactation , Health Behavior , Nitrogen Isotopes , Cetacea
3.
PLoS Pathog ; 19(4): e1011317, 2023 04.
Article in English | MEDLINE | ID: mdl-37071661

ABSTRACT

Metabolism is key to cellular processes that underlie the ability of a virus to productively infect. Polyamines are small metabolites vital for many host cell processes including proliferation, transcription, and translation. Polyamine depletion also inhibits virus infection via diverse mechanisms, including inhibiting polymerase activity and viral translation. We showed that Coxsackievirus B3 (CVB3) attachment requires polyamines; however, the mechanism was unknown. Here, we report polyamines' involvement in translation, through a process called hypusination, promotes expression of cholesterol synthesis genes by supporting SREBP2 synthesis, the master transcriptional regulator of cholesterol synthesis genes. Measuring bulk transcription, we find polyamines support expression of cholesterol synthesis genes, regulated by SREBP2. Thus, polyamine depletion inhibits CVB3 by depleting cellular cholesterol. Exogenous cholesterol rescues CVB3 attachment, and mutant CVB3 resistant to polyamine depletion exhibits resistance to cholesterol perturbation. This study provides a novel link between polyamine and cholesterol homeostasis, a mechanism through which polyamines impact CVB3 infection.


Subject(s)
Coxsackievirus Infections , Enterovirus Infections , Enterovirus , Humans , Enterovirus/metabolism , Polyamines/metabolism , Virus Replication , Enterovirus B, Human
4.
Mar Pollut Bull ; 191: 114901, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37058830

ABSTRACT

Active biomonitoring of chemical contamination (e.g., Cd, Hg, Pb, DDT, PCB, PAH) in French Mediterranean coastal waters has been performed for more than two decades. This study aimed at presenting the current contamination in 2021 and the temporal evolution of concentrations from 2000. Based on a relative spatial comparison, low concentrations were measured in 2021 at most sites (>83 %). Also, several stations with moderate to high levels were highlighted in the vicinity of major urban industrial centers (e.g., Marseille, Toulon) and near river mouths (e.g., Rhône, Var). Over the last 20 years, no major trend was revealed, mostly, especially for the relative high-level sites. This likely constant contamination over time, plus slight increases of metallic elements at a few sites, still raise questions on the efforts that remain to be made. The decreasing trends of organic compounds, in particular PAH, provide evidence of the efficiency of some management actions.


Subject(s)
Mytilus , Polychlorinated Biphenyls , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/analysis , Mytilus/chemistry , Environmental Monitoring , Polychlorinated Biphenyls/analysis , Seafood
5.
Med. intensiva (Madr., Ed. impr.) ; 47(4): 203-211, abr. 2023. ilus
Article in English | IBECS | ID: ibc-218040

ABSTRACT

Objective To determinate the adherence and barriers of our early mobilization protocol in patients who had received mechanical ventilation >48h in routine daily practice through clinical information system during all Intensive Care Unit (ICU) stay. Design Observational and prospective cohort study. Setting Polyvalent ICU over a three-year period (2017–2019). Patients Adult patients on mechanical ventilation >48h who met the inclusion criteria for the early mobilization protocol. Interventions None. Main variables of interest Demographics, adherence to the protocol and putative hidden adherence, total number of mobilizations, barriers, artificial airway/ventilatory support at each mobilization level and adverse events. Results We analyzed 3269 stay-days from 388 patients with median age of 63 (51–72) years, median APACHE II 23 (18–29) and median ICU stay of 10.1 (6.2–16.5) days. Adherence to the protocol was 56.6% (1850 stay-days), but patients were mobilized in only 32.2% (1472) of all stay-days. The putative hidden adherence was 15.6% (509 stay-days) which would increase adherence to 72.2%. The most common reasons for not mobilizing patients were failure to meeting the criteria for clinical stability in 241 (42%) stay-days and unavailability of physiotherapists in 190 (33%) stay-days. Adverse events occurred in only 6 (0.4%) stay-days. Conclusions Data form Clinical Information System showed although adherence was high, patients were mobilized in only one-third of all stay-days. Knowing the specific reason why patient were not mobilized in each stay-day allow to develop concrete decisions to increase the number of mobilizations (AU)


Objetivo Determinar la adherencia y barreras del protocolo de movilización precoz en pacientes que recibieron ventilación mecánica >48 horas en la práctica diaria habitual a través del sistema de información clínica durante toda su estancia en Unidad de Cuidados Intensivos (UCI). Diseño Estudio observacional y prospectivo. Ámbito UCI polivalente durante un periodo de tres años (2017-2019). Pacientes Se incluyeron pacientes adultos en ventilación mecánica > 48 horas que cumplieron los criterios de inclusión del protocolo. Intervenciones Ninguna. Variables principales Se aplicaron variables demográficas, adherencia y adherencia oculta, número total de movilizaciones, barreras, tipo vía aérea artificial/soporte ventilatorio en cada nivel de movilización y eventos adversos. Resultados Analizamos 3.269 días de estancia de 388 pacientes con una mediana de edad de 63 (51-72) años, mediana de APACHE-II 23(18-29) y estancia en UCI mediana de 10,1 (6,2-16,5) días. La adherencia al protocolo fue del 56,6% (1.850 días de estancia), pero los pacientes se movilizaron solo el 32,2% (1.472) de todos los días de estancia. La adherencia oculta fue del 15,6% (509 días de estancia), aumentando la adherencia al 72,2%. Las causas más comunes para la no movilización fueron el incumplimiento de los criterios de estabilidad clínica en 241 (42%) días de estancia y la falta de disponibilidad de fisioterapeutas en 190 (33%) días de estancia. Los eventos adversos ocurrieron en solo 6 (0,4%) días de estancia. Conclusiones Aunque la adherencia fue alta, los pacientes se movilizaron en solo un tercio de todos los días de estancia. Conocer el motivo específico por el cual los pacientes no fueron movilizados permite desarrollar decisiones concretas para incrementar el número de movilizaciones (AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Intensive Care Units , Respiration, Artificial , Guideline Adherence , Early Ambulation , Length of Stay , Prospective Studies
6.
Med Intensiva (Engl Ed) ; 47(4): 203-211, 2023 04.
Article in English | MEDLINE | ID: mdl-36344338

ABSTRACT

OBJECTIVE: To determinate the adherence and barriers of our early mobilization protocol in patients who had received mechanical ventilation >48h in routine daily practice through clinical information system during all Intensive Care Unit (ICU) stay. DESIGN: Observational and prospective cohort study. SETTING: Polyvalent ICU over a three-year period (2017-2019). PATIENTS: Adult patients on mechanical ventilation >48h who met the inclusion criteria for the early mobilization protocol. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographics, adherence to the protocol and putative hidden adherence, total number of mobilizations, barriers, artificial airway/ventilatory support at each mobilization level and adverse events. RESULTS: We analyzed 3269 stay-days from 388 patients with median age of 63 (51-72) years, median APACHE II 23 (18-29) and median ICU stay of 10.1 (6.2-16.5) days. Adherence to the protocol was 56.6% (1850 stay-days), but patients were mobilized in only 32.2% (1472) of all stay-days. The putative hidden adherence was 15.6% (509 stay-days) which would increase adherence to 72.2%. The most common reasons for not mobilizing patients were failure to meeting the criteria for clinical stability in 241 (42%) stay-days and unavailability of physiotherapists in 190 (33%) stay-days. Adverse events occurred in only 6 (0.4%) stay-days. CONCLUSIONS: Data form Clinical Information System showed although adherence was high, patients were mobilized in only one-third of all stay-days. Knowing the specific reason why patient were not mobilized in each stay-day allow to develop concrete decisions to increase the number of mobilizations.


Subject(s)
Early Ambulation , Intensive Care Units , Adult , Humans , Middle Aged , Aged , Prospective Studies , Early Ambulation/methods , Length of Stay , Information Systems , Observational Studies as Topic
7.
BMC Genomics ; 23(1): 787, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36451099

ABSTRACT

BACKGROUND: Sitting at the interface of gene expression and host-pathogen interaction, polymerase associated factor 1 complex (PAF1C) is a rising player in the innate immune response. The complex localizes to the nucleus and associates with chromatin to modulate RNA polymerase II (RNAPII) elongation of gene transcripts. Performing this function at both proximal and distal regulatory elements, PAF1C interacts with many host factors across such sites, along with several microbial proteins during infection. Therefore, translating the ubiquity of PAF1C into specific impacts on immune gene expression remains especially relevant. RESULTS: Advancing past work, we treat PAF1 knockout cells with a slate of immune stimuli to identify key trends in PAF1-dependent gene expression with broad analytical depth. From our transcriptomic data, we confirm PAF1 is an activator of traditional immune response pathways as well as other cellular pathways correlated with pathogen defense. With this model, we employ computational approaches to refine how PAF1 may contribute to both gene activation and suppression. Specifically focusing on transcriptional motifs and regulons, we predict gene regulatory elements strongly associated with PAF1, including those implicated in an immune response. Overall, our results suggest PAF1 is involved in innate immunity at several distinct axes of regulation. CONCLUSIONS: By identifying PAF1-dependent gene expression across several pathogenic contexts, we confirm PAF1C to be a key mediator of innate immunity. Combining these transcriptomic profiles with potential regulatory networks corroborates the previously identified functions of PAF1C. With this, we foster new avenues for its study as a regulator of innate immunity, and our results will serve as a basis for targeted study of PAF1C in future validation studies.


Subject(s)
Gene Expression Profiling , Transcriptome , Immunity, Innate/genetics , Regulon , Chromatin
8.
PLoS Pathog ; 17(11): e1010100, 2021 11.
Article in English | MEDLINE | ID: mdl-34797876

ABSTRACT

Dengue virus (DENV) disruption of the innate immune response is critical to establish infection. DENV non-structural protein 5 (NS5) plays a central role in this disruption, such as antagonism of STAT2. We recently found that DENV serotype 2 (DENV2) NS5 interacts with Polymerase associated factor 1 complex (PAF1C). The primary members of PAF1C are PAF1, LEO1, CTR9, and CDC73. This nuclear complex is an emerging player in the immune response. It promotes the expression of many genes, including genes related to the antiviral, antimicrobial and inflammatory responses, through close association with the chromatin of these genes. Our previous work demonstrated that NS5 antagonizes PAF1C recruitment to immune response genes. However, it remains unknown if NS5 antagonism of PAF1C is complementary to its antagonism of STAT2. Here, we show that knockout of PAF1 enhances DENV2 infectious virion production. By comparing gene expression profiles in PAF1 and STAT2 knockout cells, we find that PAF1 is necessary to express immune response genes that are STAT2-independent. Finally, we mapped the viral determinants for the NS5-PAF1C protein interaction. We found that NS5 nuclear localization and the C-terminal region of the methyltransferase domain are required for its interaction with PAF1C. Mutation of these regions rescued the expression of PAF1-dependent immune response genes that are antagonized by NS5. In sum, our results support a role for PAF1C in restricting DENV2 replication that NS5 antagonizes through its protein interaction with PAF1C.


Subject(s)
Dengue/virology , Mutation , Protein Interaction Domains and Motifs , STAT2 Transcription Factor/metabolism , Subcellular Fractions/metabolism , Transcription Factors/metabolism , Viral Nonstructural Proteins/metabolism , A549 Cells , CRISPR-Cas Systems , Dengue/genetics , Dengue/metabolism , Dengue Virus/physiology , Humans , RNA-Seq , STAT2 Transcription Factor/antagonists & inhibitors , STAT2 Transcription Factor/genetics , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Viral Nonstructural Proteins/genetics
9.
Sci Rep ; 11(1): 4638, 2021 02 25.
Article in English | MEDLINE | ID: mdl-33633261

ABSTRACT

Stable isotopes of carbon and nitrogen characterize trophic relationships in predator-prey relationships, with clear differences between consumer and diet (discrimination factor Δ13C and Δ15N). However, parasite-host isotopic relationships remain unclear, with Δ13C and Δ15N remaining incompletely characterized, especially for helminths. In this study, we used stable isotopes to determine discrimination factors for 13 parasite-host pairings of helminths in coral reef fish. Differences in Δ15N values grouped according to parasite groups and habitat within the host with positive Δ15N values observed for trematodes and nematodes from the digestive tract and variable Δ15N values observed for cestodes and nematodes from the general cavity. Furthermore, Δ13C values showed more complex patterns with no effect of parasite group or habitat within host. A negative relationship was observed between Δ15N and host δ15N values among different host-parasite pairings as well as within 7 out of the 13 pairings, indicating that host metabolic processing affects host-parasite discrimination values. In contrast, no relationships were observed for Δ13C values. Our results indicate that parasite group, habitat within host, and host stable isotope value drive Δ15N of helminths in coral reef fish while their effect on Δ13C is more idiosyncratic. These results call for use of taxon- or species-specific and scaled framework for bulk stable isotopes in the trophic ecology of parasites.


Subject(s)
Coral Reefs , Ecosystem , Fishes/parasitology , Helminths/pathogenicity , Animals , Host-Parasite Interactions , Isotopes/analysis
10.
Nanomaterials (Basel) ; 10(12)2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33297306

ABSTRACT

Calcium phosphate-base materials (e.g., alpha tri-calcium phosphate (α-TCP)) have been shown to promote osteogenic differentiation of stem/progenitor cells, enhance osteoblast osteogenic activity and mediate in vivo bone tissue formation. However, variable particle size and hydrophilicity of the calcium phosphate result in an extremely low bioavailability. Therefore, an effective delivery system is required that can encapsulate the calcium phosphate, improve cellular entry and, consequently, elicit a potent osteogenic response in osteoblasts. In this study, collagenous matrix deposition and extracellular matrix mineralization of osteoblast lineage cells were assessed to investigate osteogenesis following intracellular delivery of α-TCP nanoparticles. The nanoparticles were formed via condensation with a novel, cationic 30 mer amphipathic peptide (RALA). Nanoparticles prepared at a mass ratio of 5:1 demonstrated an average particle size of 43 nm with a zeta potential of +26 mV. The average particle size and zeta potential remained stable for up to 28 days at room temperature and across a range of temperatures (4-37 °C). Cell viability decreased 24 h post-transfection following RALA/α-TCP nanoparticle treatment; however, recovery ensued by Day 7. Immunocytochemistry staining for Type I collagen up to Day 21 post-transfection with RALA/α-TCP nanoparticles (NPs) in MG-63 cells exhibited a significant enhancement in collagen expression and deposition compared to an untreated control. Furthermore, in porcine mesenchymal stem cells (pMSCs), there was enhanced mineralization compared to α-TCP alone. Taken together these data demonstrate that internalization of RALA/α-TCP NPs elicits a potent osteogenic response in both MG-63 and pMSCs.

11.
Biomed Mater ; 14(6): 065008, 2019 09 20.
Article in English | MEDLINE | ID: mdl-31539364

ABSTRACT

Using the layer-by-layer (LbL) assembly technique to deposit mechanically reinforcing coatings onto porous templates is a route for fabricating engineered bone scaffold materials with a combination of high porosity, strength, and stiffness. LbL assembly involves the sequential deposition of nano- to micro-scale multilayer coatings from aqueous solutions. Here, a design of experiments (DOE) approach was used to evaluate LbL assembly of polyethyleneimine (PEI), polyacrylic acid (PAA), and nanoclay coatings onto open-cell polyurethane foam templates. The thickness of the coatings, and the porosity, elastic modulus and collapse stress of coated foam templates were most strongly affected by the pH of PAA solutions, salt concentration, and interactions between these factors. The mechanical properties of coated foams correlated with the thickness of the coatings, but were also ascribed to changes in the coating properties due to the different assembly conditions. A DOE optimization aimed to balance the trade-off between higher mechanical properties but lower porosity of foam templates with increasing coating thickness. Micromechanical modeling predicted that deposition of 116 QLs would achieve mechanical properties of cancellous bone (>0.05 GPa stiffness and >2 MPa strength) at a suitable porosity of >70%. When capped with a final layer of PAA and cross-linked via thermal treatment, the PEI/PAA/PEI/nanoclay coatings exhibited good indirect cytotoxicity with mesenchymal stem cells. The ability of LbL assembly to deposit a wide range of functional constituents within multilayer-structured coatings makes the general strategy of templated LbL assembly a powerful route for fabricating engineered tissue scaffolds that can be applied onto various porous template materials to achieve a wide range of properties, pore structures, and multifunctionality.


Subject(s)
Bone and Bones/physiology , Nanocomposites/chemistry , Tissue Engineering/methods , Acrylic Resins/chemistry , Animals , Anti-Bacterial Agents/chemistry , Biomimetic Materials/chemistry , Bone Marrow Cells/cytology , Coated Materials, Biocompatible/chemistry , Compressive Strength , Cross-Linking Reagents/chemistry , Elasticity , Hydrogen-Ion Concentration , Materials Testing , Mesenchymal Stem Cells/cytology , Polyethyleneimine/chemistry , Porosity , Stress, Mechanical , Swine , Tissue Scaffolds/chemistry , Titanium/chemistry , X-Ray Microtomography
12.
Metabolomics ; 15(1): 11, 2019 01 08.
Article in English | MEDLINE | ID: mdl-30830456

ABSTRACT

INTRODUCTION: Untargeted metabolomics is a powerful tool to detect hundreds of metabolites within a given tissue and to compare the metabolite composition of samples in a comprehensive manner. However, with regard to pollen research such comprehensive metabolomics approaches are yet not well developed. To enable isolation of pollen that is tightly enclosed within the anthers of the flower, such as immature pollen, the current pollen isolation protocols require the use of a watery solution. These protocols raise a number of concerns for their suitability in metabolomics analyses, in view of possible metabolic activities in the pollen and contamination with anther metabolites. OBJECTIVES: We assessed the effect of different sample preparation procedures currently used for pollen isolation for their suitability to perform metabolomics of tomato pollen. METHODS: Pollen were isolated using different methods and the metabolic profiles were analysed by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Our results demonstrated that pollen isolation in a watery solution led to (i) rehydration of the pollen grains, inducing marked metabolic changes in flavonoids, phenylpropanoids and amino acids and thus resulting in a metabolite profile that did not reflect the one of mature dry pollen, (ii) hydrolysis of sucrose into glucose and fructose during subsequent metabolite extraction, unless the isolated and rehydrated pollen were lyophilized prior to extraction, and (iii) contamination with anther-specific metabolites, such as alkaloids, thus compromising the metabolic purity of the pollen fraction. CONCLUSION: We conclude that the current practices used to isolate pollen are suboptimal for metabolomics analyses and provide recommendations on how to improve the pollen isolation protocol, in order to obtain the most reliable metabolic profile from pollen tissue.


Subject(s)
Pollen/metabolism , Solanum lycopersicum/metabolism , Specimen Handling/methods , Alkaloids/metabolism , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Mass Spectrometry/methods , Metabolome , Metabolomics/methods
13.
J Fish Biol ; 94(1): 53-61, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30367721

ABSTRACT

This study used otolith microchemistry to evaluate whether the moray eel Gymnothorax chilospilus uses different habitats throughout its life (mainly juvenile and adult phases). Of the most informative trace elements within otoliths (the twelve isotopes 23 Na, 25 Mg, 43 Ca, 55 Mn, 59 Co, 60 Ni, 63 Cu, 66 Zn, 86 Sr, 111 Cd, 138 Ba and 208 Pb) only three ratios of Ca (Na:Ca, Sr:Ca and Ba:Ca) were informative and therefore used in a multivariate regression-tree analysis. Using a multivariate partitioning, three main phases were described from profiles, including the larval life phase (leptocephali), the intermediate phase (longest section between the larval life phase and the terminal phase) and the terminal phase (final section i.e., the most recent months preceding the death of fish). According to concentrations of the three ratios to Ca, G. chilospilus can be separated into three groups during their larval life stage (very different in Sr and Na), four groups during the intermediate phase (few differences in Sr and Na) and three groups during the terminal phase (differences in Sr), illustrating that G. chilospilus inhabit different habitats during these three phases. Our results showed that the leptocephali encountered different oceanic water masses with fluctuating Sr:Ca ratios during the early larval phase. During the intermediate phase (main part of their life-span), they lived in lagoonal waters such as fringing reefs or reef flats of lagoonal islets, characterized by a lower Sr:Ca ratio. During the latter part of their life, approximately one third of G. chilospilus encountered more oceanic waters close to or at barrier reefs, suggesting possible movements of these fish along a coast-to-ocean gradient.


Subject(s)
Behavior, Animal , Coral Reefs , Ecosystem , Eels/physiology , Animals , Multivariate Analysis , Otolithic Membrane/chemistry , Seafood , Trace Elements/analysis
15.
Cell ; 175(7): 1931-1945.e18, 2018 12 13.
Article in English | MEDLINE | ID: mdl-30550790

ABSTRACT

Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells. Finally, we identified a ZIKV-specific interaction between NS4A and ANKLE2, a gene linked to hereditary microcephaly, and showed that ZIKV NS4A causes microcephaly in Drosophila in an ANKLE2-dependent manner. Thus, comparative flavivirus-host PPI mapping provides biological insights and, when coupled with in vivo models, can be used to unravel pathogenic mechanisms.


Subject(s)
Dengue Virus , Dengue , Membrane Proteins , Nuclear Proteins , Viral Nonstructural Proteins , Zika Virus Infection , Zika Virus , Animals , Cell Line, Tumor , Culicidae , Dengue/genetics , Dengue/metabolism , Dengue/pathology , Dengue Virus/genetics , Dengue Virus/metabolism , Dengue Virus/pathogenicity , HEK293 Cells , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Protein Interaction Mapping , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Zika Virus/genetics , Zika Virus/metabolism , Zika Virus/pathogenicity , Zika Virus Infection/genetics , Zika Virus Infection/metabolism , Zika Virus Infection/pathology
16.
Sci Total Environ ; 612: 1091-1104, 2018 Jan 15.
Article in English | MEDLINE | ID: mdl-28892853

ABSTRACT

The integration, accumulation and transfer of trace elements across the main tropic levels of many food webs are poorly documented. This is notably the case for the complex trophic webs of coral reef ecosystems. Our results show that in the south-west lagoon of New Caledonia both abiotic (i.e. sediments) and biotic (i.e. primary producers, consumers and predators) compartments are contaminated by trace elements. However, our analyses revealed different contamination patterns from the sources of organic matter to the predators. The trophic levels involved in the sedimentary benthic food web (S-BFW, based on the sedimentary organic matter) and to a lesser extent in the reef benthic food web (R-BFW, based on algal turf) were mainly contaminated by trace elements that originate from mining activities like Ni and associated trace elements (Co, Cr, Fe, and Mn). Trace elements linked to agro-industrial (As, Hg, and Zn) and urban (Ag, Cd, Cu, Pb, Se, and V) activities were also integrated into the S-BFW, but preferentially into the R-BFW, and to a lesser extent into the detrital benthic food web (D-BFW, supplied by sea-grass plants). Most of the trace elements were biodiminished with increasing trophic levels along food webs. However, a marked biomagnification was observed for Hg, and suspected for Se and Zn. These results provide important baseline information to better interpret trace element contamination in the different organisms and trophic levels in a highly diversified coral reef lagoon.


Subject(s)
Coral Reefs , Environmental Monitoring , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Food Chain , New Caledonia
17.
Article in English | MEDLINE | ID: mdl-30666300

ABSTRACT

Studying how arthropod-borne viruses interact with their arthropod vectors is critical to understanding how these viruses replicate and are transmitted. Until recently, these types of studies were limited in scale because of the lack of classical tools available to study virus-host interaction for non-model viruses and non-model organisms. Advances in systems biology "-omics"-based techniques such as next-generation sequencing (NGS) and mass spectrometry can rapidly provide an unbiased view of arbovirus-vector interaction landscapes. In this mini-review, we discuss how arbovirus-vector interaction studies have been advanced by systems biology. We review studies of arbovirus-vector interactions that occur at multiple time and length scales, including intracellular interactions, interactions at the level of the organism, viral and vector populations, and how new techniques can integrate systems-level data across these different scales.


Subject(s)
Arboviruses/growth & development , Arthropod Vectors/immunology , Arthropod Vectors/virology , Host Microbial Interactions , Systems Biology/methods , Animals , High-Throughput Nucleotide Sequencing/methods , Mass Spectrometry/methods
18.
Parasitol Int ; 66(6): 837-840, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28797592

ABSTRACT

Nematodes belonging to the genus Anisakis are important parasites due to their abundance in seafood and health impacts on humans. In the present study Anisakis larvae were found in a number of uncommon hosts including the Grey petrel, Procellaria cinerea, the Little penguin, Eudyptula minor, Blue-lipped sea krait, Laticauda laticaudata and Spinner shark, Carcharhinus brevipinna. Morphological examination showed nematodes in these animals are Anisakis larval type I. Genetic characterisation suggested that the larva from one Grey petrel was Anisakis berlandi, whereas the other larvae from the second Grey petrel and from the little penguin were Anisakis pegreffii. A number of larvae found in Blue-lipped sea krait and Spinner shark were identified as Anisakis typica. This is the first report of infective stage of Anisakis larvae parasitising hosts other than teleost fish. Understanding of the extent of infection and the pathogenicity of anisakid nematodes in hosts found in the present study is important in the conservation studies and management plans of these hosts.


Subject(s)
Anisakiasis/veterinary , Anisakis/physiology , Bird Diseases/parasitology , Birds , Fish Diseases/parasitology , Sharks , Snakes , Animals , Anisakiasis/parasitology , Anisakis/anatomy & histology , Anisakis/genetics , Anisakis/growth & development , Host-Parasite Interactions , Larva/anatomy & histology , Larva/genetics , Larva/growth & development , Larva/physiology , New Caledonia , Spheniscidae , Victoria
19.
Plant Reprod ; 30(2): 81-94, 2017 06.
Article in English | MEDLINE | ID: mdl-28508929

ABSTRACT

KEY MESSAGE: Pollen development metabolomics. Developing pollen is among the plant structures most sensitive to high temperatures, and a decrease in pollen viability is often associated with an alteration of metabolite content. Most of the metabolic studies of pollen have focused on a specific group of compounds, which limits the identification of physiologically important metabolites. To get a better insight into pollen development and the pollen heat stress response, we used a liquid chromatography-mass spectrometry platform to detect secondary metabolites in pollen of tomato (Solanum lycopersicum L.) at three developmental stages under control conditions and after a short heat stress at 38 °C. Under control conditions, the young microspores accumulated a large amount of alkaloids and polyamines, whereas the mature pollen strongly accumulated flavonoids. The heat stress treatment led to accumulation of flavonoids in the microspore. The biological role of the detected metabolites is discussed. This study provides the first untargeted metabolomic analysis of developing pollen under a changing environment that can serve as reference for further studies.


Subject(s)
Heat-Shock Response , Pollen/growth & development , Solanum lycopersicum/metabolism , Alkaloids/metabolism , Chromatography, Gas , Chromatography, Liquid , Flavonoids/metabolism , Solanum lycopersicum/cytology , Metabolomics , Pollen/metabolism , Polyamines/metabolism , Secondary Metabolism
20.
Expert Opin Ther Targets ; 20(9): 1075-85, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26942553

ABSTRACT

INTRODUCTION: Development of a therapy for bone metastases is of paramount importance for castration-resistant prostate cancer (CRPC). The osteomimetic properties of CRPC confer a propensity to metastasize to osseous sites. Micro-ribonucleic acid (miRNA) is non-coding RNA that acts as a post-transcriptional regulator of multiple proteins and associated pathways. Therefore identification of miRNAs could reveal a valid third generation therapy for CRPC. AREAS COVERED: miR34a has been found to play an integral role in the progression of prostate cancer, particularly in the regulation of metastatic genes involved in migration, intravasation, extravasation, bone attachment and bone homeostasis. The correlation between miR34a down-regulation and metastatic progression has generated substantial interest in this field. EXPERT OPINION: Examination of the evidence reveals that miR34a is an ideal target for gene therapy for metastatic CRPC. We also conclude that future studies should focus on the effects of miR34a upregulation in CRPC with respect to migration, translocation to bone micro-environment and osteomimetic phenotype development. The success of miR34a as a therapeutic is reliant on the development of appropriate delivery systems and targeting to the bone micro-environment. In tandem with any therapeutic studies, biomarker serum levels should also be ascertained as an indicator of successful miR34a delivery.


Subject(s)
Bone Neoplasms/therapy , MicroRNAs/genetics , Prostatic Neoplasms, Castration-Resistant/therapy , Animals , Biomarkers, Tumor/blood , Bone Neoplasms/genetics , Bone Neoplasms/secondary , Disease Progression , Down-Regulation , Genetic Therapy/methods , Humans , Male , MicroRNAs/administration & dosage , Prostatic Neoplasms, Castration-Resistant/genetics , Tumor Microenvironment
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