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1.
PLoS Biol ; 21(2): e3001887, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36802386

RESUMO

Outbreaks of the Eurasian spruce bark beetle (Ips typographus) have decimated millions of hectares of conifer forests in Europe in recent years. The ability of these 4.0 to 5.5 mm long insects to kill mature trees over a short period has been sometimes ascribed to two main factors: (1) mass attacks on the host tree to overcome tree defenses and (2) the presence of fungal symbionts that support successful beetle development in the tree. While the role of pheromones in coordinating mass attacks has been well studied, the role of chemical communication in maintaining the fungal symbiosis is poorly understood. Previous evidence indicates that I. typographus can distinguish fungal symbionts of the genera Grosmannia, Endoconidiophora, and Ophiostoma by their de novo synthesized volatile compounds. Here, we hypothesize that the fungal symbionts of this bark beetle species metabolize spruce resin monoterpenes of the beetle's host tree, Norway spruce (Picea abies), and that the volatile products are used as cues by beetles for locating breeding sites with beneficial symbionts. We show that Grosmannia penicillata and other fungal symbionts alter the profile of spruce bark volatiles by converting the major monoterpenes into an attractive blend of oxygenated derivatives. Bornyl acetate was metabolized to camphor, and α- and ß-pinene to trans-4-thujanol and other oxygenated products. Electrophysiological measurements showed that I. typographus possesses dedicated olfactory sensory neurons for oxygenated metabolites. Both camphor and trans-4-thujanol attracted beetles at specific doses in walking olfactometer experiments, and the presence of symbiotic fungi enhanced attraction of females to pheromones. Another co-occurring nonbeneficial fungus (Trichoderma sp.) also produced oxygenated monoterpenes, but these were not attractive to I. typographus. Finally, we show that colonization of fungal symbionts on spruce bark diet stimulated beetles to make tunnels into the diet. Collectively, our study suggests that the blends of oxygenated metabolites of conifer monoterpenes produced by fungal symbionts are used by walking bark beetles as attractive or repellent cues to locate breeding or feeding sites containing beneficial microbial symbionts. The oxygenated metabolites may aid beetles in assessing the presence of the fungus, the defense status of the host tree and the density of conspecifics at potential feeding and breeding sites.


Assuntos
Besouros , Picea , Gorgulhos , Animais , Feminino , Monoterpenos/análise , Monoterpenos/metabolismo , Árvores/microbiologia , Cânfora/análise , Cânfora/metabolismo , Casca de Planta/química , Casca de Planta/metabolismo , Casca de Planta/microbiologia , Melhoramento Vegetal , Besouros/fisiologia , Picea/química , Picea/metabolismo , Picea/microbiologia , Feromônios/metabolismo
2.
Mol Biol Evol ; 41(10)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39288326

RESUMO

Chemical communication using pheromones is thought to have contributed to the diversification and speciation of insects. The species-specific pheromones are detected by specialized pheromone receptors (PRs). Whereas the evolution and function of PRs have been extensively studied in Lepidoptera, only a few PRs have been identified in beetles, which limits our understanding of their evolutionary histories and physiological functions. To shed light on these questions, we aimed to functionally characterize potential PRs in the spruce bark beetle Ips typographus ("Ityp") and explore their evolutionary origins and molecular interactions with ligands. Males of this species release an aggregation pheromone comprising 2-methyl-3-buten-2-ol and (4S)-cis-verbenol, which attracts both sexes to attacked trees. Using two systems for functional characterization, we show that the highly expressed odorant receptor (OR) ItypOR41 responds specifically to (4S)-cis-verbenol, with structurally similar compounds eliciting minor responses. We next targeted the closely related ItypOR40 and ItypOR45. Whereas ItypOR40 was unresponsive, ItypOR45 showed an overlapping response profile with ItypOR41, but a broader tuning. Our phylogenetic analysis shows that these ORs are present in a different OR clade as compared to all other known beetle PRs, suggesting multiple evolutionary origins of PRs in bark beetles. Next, using computational analyses and experimental validation, we reveal two amino acid residues (Gln179 and Trp310) that are important for ligand binding and pheromone specificity of ItypOR41 for (4S)-cis-verbenol, possibly via hydrogen bonding to Gln179. Collectively, our results shed new light on the origins, specificity, and ligand binding mechanisms of PRs in beetles.


Assuntos
Besouros , Evolução Molecular , Filogenia , Receptores de Feromônios , Animais , Besouros/genética , Besouros/metabolismo , Receptores de Feromônios/genética , Receptores de Feromônios/metabolismo , Masculino , Feromônios/metabolismo , Feminino , Monoterpenos/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Evolução Biológica , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Monoterpenos Bicíclicos
3.
Nano Lett ; 24(40): 12529-12535, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39348627

RESUMO

Gold nanoparticles possess unique photothermal properties and have gained considerable interest in biomedical research, particularly for photothermal therapy (PTT). This study focuses on evaluating the photothermal properties of gold nanorods (AuNRs) supported on glass substrates upon excitation with near-infrared (NIR) light. Two aspect ratios of AuNRs were electrostatically immobilized onto glass with controlled coverage. In situ X-ray diffraction (XRD) was performed to evaluate the photothermal behavior and morphological changes of the supported AuNRs during NIR laser irradiation. The XRD data sets were corroborated with scanning electron microscopy and Vis-NIR spectroscopy characterization. XRD revealed a linear temperature increase with laser power, aligning with theoretical predictions, and a slope dependent on the AuNR coverage, until the onset of morphology transformations around 120 °C. This study provides valuable insights into the photothermal properties of supported AuNRs, crucial for their application in PTT.

4.
BMC Genomics ; 25(1): 764, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107741

RESUMO

BACKGROUND: Chemoreception is crucial for insect fitness, underlying for instance food-, host-, and mate finding. Chemicals in the environment are detected by receptors from three divergent gene families: odorant receptors (ORs), gustatory receptors (GRs), and ionotropic receptors (IRs). However, how the chemoreceptor gene families evolve in parallel with ecological specializations remains poorly understood, especially in the order Coleoptera. Hence, we sequenced the genome and annotated the chemoreceptor genes of the specialised ambrosia beetle Trypodendron lineatum (Coleoptera, Curculionidae, Scolytinae) and compared its chemoreceptor gene repertoires with those of other scolytines with different ecological adaptations, as well as a polyphagous cerambycid species. RESULTS: We identified 67 ORs, 38 GRs, and 44 IRs in T. lineatum ('Tlin'). Across gene families, T. lineatum has fewer chemoreceptors compared to related scolytines, the coffee berry borer Hypothenemus hampei and the mountain pine beetle Dendroctonus ponderosae, and clearly fewer receptors than the polyphagous cerambycid Anoplophora glabripennis. The comparatively low number of chemoreceptors is largely explained by the scarcity of large receptor lineage radiations, especially among the bitter taste GRs and the 'divergent' IRs, and the absence of alternatively spliced GR genes. Only one non-fructose sugar receptor was found, suggesting several sugar receptors have been lost. Also, we found no orthologue in the 'GR215 clade', which is widely conserved across Coleoptera. Two TlinORs are orthologous to ORs that are functionally conserved across curculionids, responding to 2-phenylethanol (2-PE) and green leaf volatiles (GLVs), respectively. CONCLUSIONS: Trypodendron lineatum reproduces inside the xylem of decaying conifers where it feeds on its obligate fungal mutualist Phialophoropsis ferruginea. Like previous studies, our results suggest that stenophagy correlates with small chemoreceptor numbers in wood-boring beetles; indeed, the few GRs may be due to its restricted fungal diet. The presence of TlinORs orthologous to those detecting 2-PE and GLVs in other species suggests these compounds are important for T. lineatum. Future functional studies should test this prediction, and chemoreceptor annotations should be conducted on additional ambrosia beetle species to investigate whether few chemoreceptors is a general trait in this specialized group of beetles.


Assuntos
Receptores Odorantes , Animais , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Besouros/genética , Filogenia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
5.
J Am Chem Soc ; 146(29): 19828-19838, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39003762

RESUMO

In recent years, methodologies that rely on water as the reaction medium have gained considerable attention. The unique properties of micellar solutions were shown to improve the regio-, stereo-, and chemoselectivity of different transformations. Herein, we demonstrate that the aqueous environment is a suitable medium for a visible light driven cobalt-catalyzed reaction involving radical species. In this system, reduced vitamin B12 reacts with alkyl halides, generating radicals that are trapped by the lipophilic olefin present in the Stern layer. A series of NMR measurements and theoretical studies revealed the location of reaction components in the micellar system.

6.
Br J Dermatol ; 190(2): 191-198, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-37776301

RESUMO

BACKGROUND: The prevalence of atopic dermatitis (AD) has increased over several decades and now affects about one-fifth of all children in high-income countries (HICs). While the increase continues in lower-income countries, the prevalence of AD might have reached a plateau in HICs. OBJECTIVES: To investigate trends in the prevalence of AD and atopic comorbidity in schoolchildren in Sweden. METHODS: The study population consisted of three cohorts of children (median age 8 years) in Norrbotten, Sweden, for 1996 (n = 3430), 2006 (n = 2585) and 2017 (n = 2785). An identical questionnaire that included questions from the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was used in all three cohorts. Trends in AD prevalence were estimated, as well as trends in atopic comorbidity. AD prevalence was estimated both according to the ISAAC definition of AD and by adding the reported diagnosis by a physician (D-AD). RESULTS: The prevalence of AD decreased in the last decade, from 22.8% (1996) and 21.3% (2006) to 16.3% (2017; P < 0.001). The prevalence of D-AD was lower, but the same pattern of decrease was seen, from 9.3% (1996) and 9.4% (2006) to 5.7% (2017; P < 0.001). In all three cohorts, AD was more common among girls than boys (18.9% vs. 13.8% in 2017; P < 0.001). Children from the mountain inlands had a higher prevalence of AD than children from coastal cities (22.0% vs. 15.1% in 2017; P < 0.001). In comparing D-AD, there were no significant differences between the sexes or between inland or coastal living. Concomitant asthma increased over the years from 12.2% (1996) to 15.8% (2006) to 23.0% (2017; P < 0.001). Concomitant allergic rhinitis and allergic sensitization increased from 1996 (15.0% and 27.5%) to 2006 (24.7% and 49.5%) but then levelled off until 2017 (21.0% and 46.7%). CONCLUSIONS: The prevalence of AD among schoolchildren in Sweden decreased over the study period, whereas atopic comorbidity among children with AD increased. Although a decrease was seen, AD is still common and the increase in atopic comorbidity among children with AD, especially the increase in asthma, is concerning.


Assuntos
Asma , Dermatite Atópica , Rinite Alérgica Sazonal , Rinite Alérgica , Criança , Masculino , Feminino , Humanos , Dermatite Atópica/epidemiologia , Suécia , Rinite Alérgica Sazonal/epidemiologia , Prevalência , Asma/epidemiologia , Inquéritos e Questionários
7.
Pediatr Allergy Immunol ; 35(4): e14120, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38556800

RESUMO

BACKGROUND: In the present study, we describe prevalence trends of asthma and investigate the association with asthma symptoms, use of asthma medication, and asthma severity among 8-year-old children in Norrbotten, Sweden in 1996, 2006, and 2017. METHODS: Within the Obstructive Lung Disease in Northern Sweden (OLIN) studies, three pediatric cohorts were recruited in 1996, 2006, and 2017 respectively. Identical methods were used; all children in first and second grade (median age 8 years) in three municipalities were invited to a parental questionnaire survey, completed by n = 3430 in 1996 (97% participation), n = 2585 in 2006 (96%), and n = 2785 in 2017 (91%). The questionnaire included questions about respiratory symptoms and diagnosis, treatment, and severity of asthma. RESULTS: The prevalence of wheezing was stable during the study, 10.1% in 1996; 10.8% in 2006; and 10.3% in 2017, p = .621, while physician-diagnosed asthma increased: 5.7%, 7.4%, and 12.2%, p < .001. The use of asthma medication in the last 12 months increased: 7.1%, 8.7%, and 11.5%, p < .001. Among children diagnosed with asthma, the prevalence of asthma symptoms, the impact on daily life, and severe asthma decreased, while the use of inhaled corticosteroids increased from 1996 until 2017. CONCLUSION: The prevalence of wheezing was stable among 8-year-old in this area from 1996 to 2017, while the prevalence of physician-diagnosed asthma doubled but without an increase in asthma morbidity. The increase of physician-diagnosed asthma without a coincident increase in asthma morbidity can partly be explained by more and earlier diagnosis among those with mild asthma.


Assuntos
Asma , Sons Respiratórios , Humanos , Criança , Prevalência , Suécia/epidemiologia , Inquéritos e Questionários
8.
Microb Cell Fact ; 23(1): 110, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609906

RESUMO

BACKGROUND: The wasabi receptor, also known as the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel, is a potential target for development of repellents for insects, like the pine weevil (Hylobius abietis) feeding on conifer seedlings and causing damage in forestry. Heterologous expression of TRPA1 from pine weevil in the yeast Pichia pastoris can potentially provide protein for structural and functional studies. Here we take advantage of the Green Fluorescent Protein (GFP) tag to examine the various steps of heterologous expression, to get more insight in clone selection, expression and isolation of the intact purified protein. RESULTS: The sequence of HaTRPA1 is reported and GFP-tagged constructs were made of the full-length protein and a truncated version (Δ1-708 HaTRPA1), lacking the N-terminal ankyrin repeat domain. Clones were screened on GFP expression plates, induced in small liquid cultures and in fed-batch cultures, and evaluated by flow cytometry and fluorescence microscopy. The screening on plates successfully identifies low-expression clones, but fails to predict the ranking of the best performing clones in small-scale liquid cultures. The two constructs differ in their cellular localization. Δ1-708 HaTRPA1 is found in a ring at the perimeter of cell, whereas HaTRPA1 is forming highly fluorescent speckles in interior regions of the cell. The pattern is consistent in different clones of the same construct and persists in fed-batch culture. The expression of Δ1-708 HaTRPA1 decreases the viability more than HaTRPA1, and in fed-batch culture it is clear that intact cells first express Δ1-708 HaTRPA1 and then become damaged. Purifications show that both constructs suffer from degradation of the expressed protein, but especially the HaTRPA1 construct. CONCLUSIONS: The GFP tag makes it possible to follow expression by flow cytometry and fluorescence microscopy. Analyses of localization, cell viability and expression show that the former two parameters are specific for each of the two evaluated constructs, whereas the relative expression of the constructs varies with the cultivation method. High expression is not all that matters, so taking damaged cells into account, something that may be linked to protein degradation, is important when picking the most suitable construct, clone, and expression scheme.


Assuntos
Saccharomycetales , Gorgulhos , Animais , Proteínas de Fluorescência Verde/genética , Citometria de Fluxo
9.
Occup Environ Med ; 81(5): 238-243, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38811167

RESUMO

OBJECTIVES: Increasing epidemiological and experimental evidence suggests that particle exposure is an environmental risk factor for chronic kidney disease (CKD). However, only a few case-control studies have investigated this association in an occupational setting. Hence, our objective was to investigate associations between particle exposure and CKD in a large cohort of Swedish construction workers. METHODS: We performed a retrospective cohort study in the Swedish Construction Workers' Cohort, recruited 1971-1993 (n=286 089). A job-exposure matrix was used to identify workers exposed to nine different particulate exposures, which were combined into three main categories (inorganic dust and fumes, wood dust and fibres). Incident CKD and start of renal replacement therapy (RRT) were obtained from validated national registries until 2021 and analysed using adjusted Cox proportional hazards models. RESULTS: Exposure to inorganic dust and fumes was associated with an increased risk of CKD and RRT during working age (adjusted HR for CKD at age <65 years 1.15, 95% CI 1.05 to 1.26). The elevated risk did not persist after retirement age. Exposure to cement dust, concrete dust and diesel exhaust was associated with CKD. Elevated HRs were also found for quartz dust and welding fumes. CONCLUSIONS: Workers exposed to inorganic particles seem to be at elevated risk of CKD and RRT. Our results are in line with previous evidence of renal effects of ambient air pollution and warrant further efforts to reduce occupational and ambient particle exposure.


Assuntos
Indústria da Construção , Poeira , Doenças Profissionais , Exposição Ocupacional , Insuficiência Renal Crônica , Humanos , Exposição Ocupacional/efeitos adversos , Suécia/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Pessoa de Meia-Idade , Masculino , Adulto , Indústria da Construção/estatística & dados numéricos , Estudos Retrospectivos , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Feminino , Idoso , Fatores de Risco , Poluentes Ocupacionais do Ar/efeitos adversos , Modelos de Riscos Proporcionais , Estudos de Coortes , Emissões de Veículos/análise , Materiais de Construção/efeitos adversos , Madeira
10.
Microsc Microanal ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38525893

RESUMO

Nanoparticles are utilized in a multitude of applications due to their unique properties. Consequently, characterization of nanoparticles is crucial, and various methods have been employed in these pursuits. One such method is Atom Probe Tomography (APT). However, existing sample preparation techniques for APT generally involve embedding of the nanoparticles in a matrix different from their environment in solutions or at solid-liquid interfaces. In this work, we demonstrate a methodology based on silica embedding and explore how it can be utilized to form a matrix for nanoparticles suitable for APT analysis. Through chemisorption to a surface, gold nanoparticles were densely packed, ensuring a high probability of encountering at least one particle in the APT analyses. The nanoparticle-covered surface was embedded in a silica film, replacing the water and thus making this method suitable for studying nanoparticles in their hydrated state. The nanoparticle's silver content and its distribution, originating from the nanoparticle synthesis, could be identified in the APT analysis. Sodium clusters, possibly originating from the sodium citrate used to stabilize the particles in solution, were observed on the nanoparticle surfaces. This indicates the potential for silica embedding to be used for studying ligands on nanoparticles in their hydrated state.

11.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673786

RESUMO

Antimicrobial peptides (AMPs) are viewed as potential compounds for the treatment of bacterial infections. Nevertheless, the successful translation of AMPs into clinical applications has been impeded primarily due to their low stability in biological environments and potential toxicological concerns at higher concentrations. The covalent attachment of AMPs to a material's surface has been sought to improve their stability. However, it is still an open question what is required to best perform such an attachment and the role of the support. In this work, six different AMPs were covalently attached to a long-ranged ordered amphiphilic hydrogel, with their antibacterial efficacy evaluated and compared to their performance when free in solution. Among the tested AMPs were four different versions of synthetic end-tagged AMPs where the sequence was altered to change the cationic residue as well as to vary the degree of hydrophobicity. Two previously well-studied AMPs, Piscidin 1 and Omiganan, were also included as comparisons. The antibacterial efficacy against Staphylococcus aureus remained largely consistent between free AMPs and those attached to surfaces. However, the activity pattern against Pseudomonas aeruginosa on hydrogel surfaces displayed a marked contrast to that observed in the solution. Additionally, all the AMPs showed varying degrees of hemolytic activity when in solution. This activity was entirely diminished, and all the AMPs were non-hemolytic when attached to the hydrogels.


Assuntos
Antibacterianos , Hemólise , Hidrogéis , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Staphylococcus aureus , Hidrogéis/química , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Hemólise/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Humanos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Interações Hidrofóbicas e Hidrofílicas , Eritrócitos/efeitos dos fármacos
12.
BMC Genomics ; 24(1): 19, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639634

RESUMO

BACKGROUND: Adaptations by arthropod pests to host plant defenses of crops determine their impacts on agricultural production. The larval host range of western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is restricted to maize and a few grasses. Resistance of D. v. virgifera to crop rotation practices and multiple insecticides contributes to its status as the most damaging pest of cultivated maize in North America and Europe. The extent to which adaptations by this pest contributes to host plant specialization remains unknown. RESULTS: A 2.42 Gb draft D. v. virgifera genome, Dvir_v2.0, was assembled from short shotgun reads and scaffolded using long-insert mate-pair, transcriptome and linked read data. K-mer analysis predicted a repeat content of ≥ 61.5%. Ortholog assignments for Dvir_2.0 RefSeq models predict a greater number of species-specific gene duplications, including expansions in ATP binding cassette transporter and chemosensory gene families, than in other Coleoptera. A majority of annotated D. v. virgifera cytochrome P450s belong to CYP4, 6, and 9 clades. A total of 5,404 transcripts were differentially-expressed between D. v. virgifera larvae fed maize roots compared to alternative host (Miscanthus), a marginal host (Panicum virgatum), a poor host (Sorghum bicolor) and starvation treatments; Among differentially-expressed transcripts, 1,908 were shared across treatments and the least number were between Miscanthus compared to maize. Differentially-expressed transcripts were enriched for putative spliceosome, proteosome, and intracellular transport functions. General stress pathway functions were unique and enriched among up-regulated transcripts in marginal host, poor host, and starvation responses compared to responses on primary (maize) and alternate hosts. CONCLUSIONS: Manual annotation of D. v. virgifera Dvir_2.0 RefSeq models predicted expansion of paralogs with gene families putatively involved in insecticide resistance and chemosensory perception. Our study also suggests that adaptations of D. v. virgifera larvae to feeding on an alternate host plant invoke fewer transcriptional changes compared to marginal or poor hosts. The shared up-regulation of stress response pathways between marginal host and poor host, and starvation treatments may reflect nutrient deprivation. This study provides insight into transcriptomic responses of larval feeding on different host plants and resources for genomic research on this economically significant pest of maize.


Assuntos
Besouros , Inseticidas , Animais , Zea mays/fisiologia , Besouros/genética , Larva/metabolismo , Poaceae/genética , Inseticidas/metabolismo , Controle Biológico de Vetores , Plantas Geneticamente Modificadas/genética , Endotoxinas
13.
Int J Cancer ; 152(4): 725-737, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36305648

RESUMO

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Pré-Escolar , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Metilação de DNA , Estudos de Casos e Controles , Estudos Prospectivos , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Biomarcadores Tumorais/metabolismo , Amianto/efeitos adversos , Marcadores Genéticos , Células Sanguíneas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia
14.
Antimicrob Agents Chemother ; 67(5): e0151922, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37098944

RESUMO

Klebsiella pneumoniae and Pseudomonas aeruginosa are two leading causes of burn and wound infections, pneumonia, urinary tract infections, and more severe invasive diseases, which are often multidrug resistant (MDR) or extensively drug resistant. Due to this, it is critical to discover alternative antimicrobials, such as bacteriophage lysins, against these pathogens. Unfortunately, most lysins that target Gram-negative bacteria require additional modifications or outer membrane permeabilizing agents to be bactericidal. We identified four putative lysins through bioinformatic analysis of Pseudomonas and Klebsiella phage genomes in the NCBI database and then expressed and tested their intrinsic lytic activity in vitro. The most active lysin, PlyKp104, exhibited >5-log killing against K. pneumoniae, P. aeruginosa, and other Gram-negative representatives of the multidrug-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, K. pneumonia, Acinetobacter baumannii, P. aeruginosa, and Enterobacter species) without further modification. PlyKp104 displayed rapid killing and high activity over a wide pH range and in high concentrations of salt and urea. Additionally, pulmonary surfactants and low concentrations of human serum did not inhibit PlyKp104 activity in vitro. PlyKp104 also significantly reduced drug-resistant K. pneumoniae >2 logs in a murine skin infection model after one treatment of the wound, suggesting that this lysin could be used as a topical antimicrobial against K. pneumoniae and other MDR Gram-negative infections.


Assuntos
Anti-Infecciosos , Bacteriófagos , Humanos , Animais , Camundongos , Pseudomonas aeruginosa , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas
15.
New Phytol ; 238(5): 1762-1770, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36880374

RESUMO

Global warming and more frequent climate extremes have caused bark beetle outbreaks of unprecedented scale of these insects in many conifer forests world-wide. Conifers that have been weakened by drought and heat or damaged by storms are highly susceptible to bark beetle infestation. A large proportion of trees with impaired defences provides good conditions for beetle population build-up of beetles, but mechanisms driving host search of pioneer beetles are still uncertain in several species, including the Eurasian spruce bark beetle Ips typographus. Despite a two-century-long history of bark beetle research, we still lack a sufficient understanding of interactions between I. typographus and its host Norway spruce (Picea abies) to forecast future disturbance regimes and forest dynamics. Depending on the scale (habitat or patch) and beetle population state (endemic or epidemic), host selection is likely driven by a combination of pre and postlanding cues, including visual selection or olfactory detection (kairomones). Here, we discuss primary attraction mechanisms and how volatile emission profiles of Norway spruce may provide cues on tree vitality and suitability for attacks by I. typographus, in particular during the endemic phase. We identify several crucial knowledge gaps and provide a research agenda addressing the experimental challenges of such investigations.


Assuntos
Besouros , Picea , Gorgulhos , Animais , Árvores , Sinais (Psicologia) , Casca de Planta
16.
Glob Chang Biol ; 29(9): 2399-2420, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36911976

RESUMO

Climate change and urbanisation are among the most pervasive and rapidly growing threats to biodiversity worldwide. However, their impacts are usually considered in isolation, and interactions are rarely examined. Predicting species' responses to the combined effects of climate change and urbanisation, therefore, represents a pressing challenge in global change biology. Birds are important model taxa for exploring the impacts of both climate change and urbanisation, and their behaviour and physiology have been well studied in urban and non-urban systems. This understanding should allow interactive effects of rising temperatures and urbanisation to be inferred, yet considerations of these interactions are almost entirely lacking from empirical research. Here, we synthesise our current understanding of the potential mechanisms that could affect how species respond to the combined effects of rising temperatures and urbanisation, with a focus on avian taxa. We discuss potential interactive effects to motivate future in-depth research on this critically important, yet overlooked, aspect of global change biology. Increased temperatures are a pronounced consequence of both urbanisation (through the urban heat island effect) and climate change. The biological impact of this warming in urban and non-urban systems will likely differ in magnitude and direction when interacting with other factors that typically vary between these habitats, such as resource availability (e.g. water, food and microsites) and pollution levels. Furthermore, the nature of such interactions may differ for cities situated in different climate types, for example, tropical, arid, temperate, continental and polar. Within this article, we highlight the potential for interactive effects of climate and urban drivers on the mechanistic responses of birds, identify knowledge gaps and propose promising future research avenues. A deeper understanding of the behavioural and physiological mechanisms mediating species' responses to urbanisation and rising temperatures will provide novel insights into ecology and evolution under global change and may help better predict future population responses.


Assuntos
Temperatura Alta , Urbanização , Animais , Cidades , Temperatura , Aves , Mudança Climática
17.
J Endovasc Ther ; : 15266028231219435, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38140719

RESUMO

OBJECTIVE: The aim of this study was to assess the risk of radiation-induced cancer development in patients that have undergone an infrarenal EVAR, stratifying the relative contributions of the procedure and the preoperative and postoperative CTAs. METHODS AND MATERIALS: The organ-specific absorbed radiation doses from CTA and the EVAR procedure were estimated from the radiation exposures of 95 and 45 male patients, respectively. Lifetime attributable risk (LAR) cancer predictions were calculated for 14 different organs. Life expectancy was assumed from a previous cohort of patients undergoing infra-renal EVAR. RESULTS: The calculated total excess cancer risk was 0.0046, ie, 1 out of 220 patients will develop a neoplasm after being exposed to the ionizing radiation from the preoperative CTA, the EVAR and annual CTA examinations for 15 years. The procedure and the preoperative CTA contributed with 38% of the total excess risk, while the rest was derived from the follow-up. If the entire CTA based follow-up would have been eliminated, an excess risk of 0.0018 (1/560) would remain. CONCLUSIONS: 1 out of 219 patients who have undergone EVAR of an infra-renal AAA have a lifetime risk of developing cancer secondary to the radiation exposures related to the procedure and the CTAs used preoperatively and during follow-up. This risk derives mostly from the yearly postoperative CTAs, underlining the potential benefits of reducing or replacing their use. CLINICAL IMPACT: A simulation-based estimation reinforced the potential deleterious effects of the radiation exposure for patients undergoing Endovascular Aneurysm Repair (EVAR) of Abdominal Aortic Aneurysms (AAA) and subsequently followed by yearly Computer Tomography Angiographies (CTAs). The risk could be as high as 1 out 219 patients developing a neoplasm after 15 years. The largest exposure derives from the follow-up CTAs and efforts to minimize their use as well as the intraoperative radiation are greatly needed. The simulation-based estimations done in this study reinforce potential deleterious effects of the radiation exposure for patients undergoing EVAR of AAA. Efforts should be done to minimize the intraoperative radiation and the number of CTAs used during follow-up.

18.
J Asthma ; 60(1): 185-194, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35167415

RESUMO

Objective: Low socioeconomic status based both on educational level and income has been associated with asthma and respiratory symptoms, but changes over time in these associations have rarely been studied. The aim was to study the associations between educational or income inequality and asthma and respiratory symptoms among women and men over a 20-year period in northern Sweden. Methods: The study was performed within the Obstructive Lung disease in Northern Sweden (OLIN) research program. Mailed questionnaire surveys were administered to a random sample of adults (20-69 years of age) living in Sweden, in 1996, 2006 and 2016. Data on educational level and income were collected from the national integrated database for labor market research. Results: The educational inequality associated with asthma and asthmatic wheeze tended to decrease from 1996 to 2016, while it increased for productive cough, the latter among men not among women. The income inequality decreased for productive cough, especially for women, while no clear overall trends were found for asthmatic wheeze and asthma, apart from a decrease in income inequality regarding asthma among men. Conclusion: The patterns for socioeconomic inequality differed for asthma and wheeze compared to productive cough, and the results emphasize that education and income do not mirror the same aspects of socioeconomic inequality in a high-income country. Our findings are important for decision makers, not the least on a political level, as reduced inequality, e.g. through education, could lead to reduced morbidity.


Assuntos
Asma , Tosse , Adulto , Masculino , Humanos , Feminino , Fatores Socioeconômicos , Renda , Escolaridade , Disparidades nos Níveis de Saúde
19.
Int Arch Occup Environ Health ; 96(9): 1283-1289, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37725195

RESUMO

OBJECTIVE: This study investigated the association between occupational physical activity (OPA) and resting blood pressure in a cohort of Swedish construction workers. METHODS: The final sample included 241,176 male construction workers. Occupations with low OPA were foremen and white-collar workers. The most frequent occupations in the medium OPA group were electricians, pipe workers, and machine operators, and in the high OPA group woodworkers, concrete workers, and painters. RESULTS: Mixed effects models showed higher systolic and lower diastolic blood pressure with higher OPA, but the associations varied depending on the year of participation and participant age as shown by significant interaction terms (OPA*age, OPA*calendar year, age*calendar year). Age-stratified linear regression analyses showed a pattern of slightly higher systolic (1.49, 95% confidence interval: 1.08-1.90 mmHg) and lower diastolic (0.89, 95% confidence interval: 0.65-1.13 mmHg) blood pressure when comparing low with high OPA, but not among the oldest age groups. CONCLUSION: Despite a rather large contrast in OPA, the differences in systolic and diastolic blood pressure according to OPA were small.

20.
BMC Biol ; 20(1): 34, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130883

RESUMO

BACKGROUND: In insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been intensively investigated in Diptera and Lepidoptera, while the functions and evolution of the more ancient IR family remain largely unexplored beyond Diptera. RESULTS: Here, we identified a repertoire of 26 IRs from transcriptomes of female and male antennae, and ovipositors in the moth Agrotis segetum. We observed that a large clade formed by IR75p and IR75q expansions is closely related to the acid-sensing IRs identified in Diptera. We functionally assayed each of the five AsegIRs from this clade using Xenopus oocytes and found that two receptors responded to the tested ligands. AsegIR75p.1 responded to several compounds but hexanoic acid was revealed to be the primary ligand, and AsegIR75q.1 responded primarily to octanoic acid, and less so to nonanoic acid. It has been reported that the C6-C10 medium-chain fatty acids repel various insects including many drosophilids and mosquitos. We show that the C6-C10 medium-chain fatty acids elicited antennal responses of both sexes of A. segetum, while only octanoic acid had repellent effect to the moths in a behavioral assay. In addition, using fluorescence in situ hybridization, we demonstrated that the five IRs and their co-receptor AsegIR8a are not located in coeloconic sensilla as found in Drosophila, but in basiconic or trichoid sensilla. CONCLUSIONS: Our results significantly expand the current knowledge of the insect IR family. Based on the functional data in combination with phylogenetic analysis, we propose that subfunctionalization after gene duplication plays an important role in the evolution of ligand specificities of the acid-sensing IRs in Lepidoptera.


Assuntos
Brassica napus , Dípteros , Mariposas , Receptores Odorantes , Animais , Antenas de Artrópodes , Caprilatos , Dípteros/genética , Feminino , Hibridização in Situ Fluorescente , Proteínas de Insetos/genética , Ligantes , Masculino , Mariposas/genética , Filogenia , Receptores Odorantes/genética
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