RESUMO
Increased mobility of chromatin surrounding double-strand breaks (DSBs) has been noted in yeast and mammalian cells but the underlying mechanism and its contribution to DSB repair remain unclear. Here, we use a telomere-based system to track DNA damage foci with high resolution in living cells. We find that the greater mobility of damaged chromatin requires 53BP1, SUN1/2 in the linker of the nucleoskeleton, and cytoskeleton (LINC) complex and dynamic microtubules. The data further demonstrate that the excursions promote non-homologous end joining of dysfunctional telomeres and implicated Nesprin-4 and kinesins in telomere fusion. 53BP1/LINC/microtubule-dependent mobility is also evident at irradiation-induced DSBs and contributes to the mis-rejoining of drug-induced DSBs in BRCA1-deficient cells showing that DSB mobility can be detrimental in cells with numerous DSBs. In contrast, under physiological conditions where cells have only one or a few lesions, DSB mobility is proposed to prevent errors in DNA repair.
Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Microtúbulos/metabolismo , Animais , Proteínas de Transporte/metabolismo , Reparo do DNA por Junção de Extremidades , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Fosforilação , Telômero , Proteínas de Ligação a Telômeros/genética , Proteínas de Ligação a Telômeros/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53RESUMO
North American river otters (Lontra canadensis) are top predators in riverine ecosystems and are vulnerable to per- and polyfluoroalkyl substance (PFAS) exposure. Little is known about the magnitude of exposure and tissue distribution of PFAS in river otters. We measured 45 PFAS in various tissues of 42 river otters collected from several watersheds in the state of West Virginia, USA. The median concentrations of ∑All (sum concentration of 45 PFAS) varied among tissues in the following decreasing order: liver (931 ng/g wet weight) > bile > pancreas > lung > kidney > blood > brain > muscle. Perfluoroalkylsulfonates (PFSAs) were the predominant compounds accounting for 58-75% of the total concentrations, followed by perfluoroalkyl carboxylates (PFCAs; 21-35%). 8:2 fluorotelomer sulfonate (8:2 FTS), 10:2 FTS, and 6:2 chlorinated polyfluoroalkyl ether sulfonate were frequently found in the liver (50-90%) and bile (96-100%), whereas hexafluoropropylene oxide dimer acid (HFPO-DA) was rarely found. The hepatic concentrations of ∑All in river otters collected downstream of a fluoropolymer production facility located along the Ohio River were 2-fold higher than those in other watersheds. The median whole body burden of ∑All was calculated to be 1580 µg. PFOS and perfluorooctanoic acid (PFOA) concentrations in whole blood of some river otters exceeded the human toxicity reference values, which warrant further studies.
Assuntos
Fluorocarbonos , Lontras , Poluentes Químicos da Água , Animais , Humanos , West Virginia , Ecossistema , Fluorocarbonos/análise , Fígado , Poluentes Químicos da Água/análiseRESUMO
High-resolution mass spectrometry (HRMS)-based suspect and nontarget screening has identified a growing number of novel per- and polyfluoroalkyl substances (PFASs) in the environment. However, without analytical standards, the fraction of overall PFAS exposure accounted for by these suspects remains ambiguous. Fortunately, recent developments in ionization efficiency (IE) prediction using machine learning offer the possibility to quantify suspects lacking analytical standards. In the present work, a gradient boosted tree-based model for predicting log IE in negative mode was trained and then validated using 33 PFAS standards. The root-mean-square errors were 0.79 (for the entire test set) and 0.29 (for the 7 PFASs in the test set) log IE units. Thereafter, the model was applied to samples of liver from pilot whales (n = 5; East Greenland) and white beaked dolphins (n = 5, West Greenland; n = 3, Sweden) which contained a significant fraction (up to 70%) of unidentified organofluorine and 35 unquantified suspect PFASs (confidence level 2-4). IE-based quantification reduced the fraction of unidentified extractable organofluorine to 0-27%, demonstrating the utility of the method for closing the fluorine mass balance in the absence of analytical standards.
Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Animais , Fluorocarbonos/análise , Poluentes Químicos da Água/análise , Espectrometria de Massas , Flúor , MamíferosRESUMO
We found highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b associated with meningoencephalitis in a stranded harbor porpoise (Phocoena phocoena). The virus was closely related to strains responsible for a concurrent avian influenza outbreak in wild birds. This case highlights the potential risk for virus spillover to mammalian hosts.
Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Phocoena , Animais , Influenza Aviária/epidemiologia , Virus da Influenza A Subtipo H5N1/genética , Suécia/epidemiologia , Mamíferos , FilogeniaRESUMO
Videos are an increasingly popular medium for supporting learning in various educational settings. Nowadays, newly designed video-based environments contain enhanced tools that allow for specific interactions with video materials (such as adding annotations and hyperlinks) which may well support generative learning and conceptual understanding. However, to exploit the potentials of such enhanced tools, we need to gain a deeper understanding on the learning processes and outcomes that go along with using these tools. Thus, we conducted a controlled laboratory experiment with 209 participants who were engaged in learning a complex topic by using different enhanced video tools (annotations vs. hyperlinks vs. control group) in different social learning settings (individual vs. collaborative learning in dyads). Findings revealed that participants who learned with hyperlinks and participants in collaborative settings created hypervideo products of higher quality than learners in other conditions. Participants who learned with annotations assessed their knowledge gain higher and had higher results in conceptual understanding when they experienced low cognitive load. With our study we contribute new original work to advance cognitive research on learning with enhanced video learning environments. Limitations and recommendations for future research are discussed.
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Temporal trends of polybrominated diphenyl ethers (PBDEs) have been extensively studied in various environmental compartments globally. However, despite the increasing use of alternative flame retardants following PBDE bans, the spatiotemporal trends of these replacements have rarely been studied, and the available results are often inconsistent. In the present study, we retrospectively investigated the spatiotemporal trends of PBDEs and a suite of alternative brominated FRs (aBFRs) and chlorinated FRs (i.e., dechloranes or DECs) in three harbor seal (Phoca vitulina) populations from the coasts of California, the Gulf of Maine, and southern Sweden during 1999-2016. We observed significantly decreasing trends of ΣPBDEs in all the three populations at an annual rate of 9-11%, which were predominantly driven by the declining concentrations of tetra- and penta-BDEs. The levels of ΣaBFRs decreased significantly in seals from California (mainly 1,3,5-tribromobenzene) and Sweden (mainly hexabromobenzene), while no trend was observed for those from Maine. By contrast, DECs (dominated by DEC 602) did not decrease significantly in any population. Compared with the consistent PBDE congener profiles across regions, aBFRs and DECs exhibited varying compositional profiles between regions, likely indicating region-specific sources of these alternative FR mixtures. Spatial analysis also revealed regional differences in the concentrations of PBDEs, aBFRs, and DECs in harbor seals. Our reconstructed spatiotemporal trends suggest the effective regulation of commercial penta-BDE mix in these regions and warrant further monitoring of the higher brominated BDEs and alternative FRs.
Assuntos
Retardadores de Chama , Phoca , Animais , Monitoramento Ambiental/métodos , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Maine , Estudos Retrospectivos , SuéciaRESUMO
Fatty acids (FAs) have been extensively used as indicators of foraging ecology in marine mammals, yet their association with exposure to contaminants has rarely been investigated. The present study provided the first characterization of the relationship between hepatic FA profiles and exposure to a suite of contaminants in a sentinel speciesâthe harbor seal (Phoca vitulina)âfrom the Gulf of Maine and the south coast of Sweden. FA profiles differed in the two seal populations, and the levels of legacy and alternative brominated flame retardants and polyhalogenated carbazoles were significantly elevated in Maine seals. Correlations between individual FAs and multiple flame retardants (FRs) and poly- and perfluoroalkyl substances (PFASs) were found in seals from both populations. Moreover, several FR and PFAS chemicals were significantly associated with the estimated desaturating enzyme activity inferred from the FA profiles. The ratios of poly to monounsaturated FAs (∑PUFAs/∑MUFAs) and those of unsaturated to saturated FAs (∑UFAs/∑SFAs) were significantly associated with HBBZ, PFHxS, or BDE 47 in seals from Maine and Sweden, whereas ∑n - 6/∑n - 3 PUFAs was significantly associated with BDE 154 and 36-CCZ in Swedish and Maine seals, respectively. Our results suggest the lipid metabolism-disrupting potential of these contaminants in marine mammals and warrant continuous biomonitoring and risk assessment, considering the critical role of PUFAs in vital biological processes.
Assuntos
Retardadores de Chama , Phoca , Poluentes Químicos da Água , Animais , Monitoramento Ambiental/métodos , Ácidos Graxos , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Poluentes Químicos da Água/análiseRESUMO
A type of monophasic group B Salmonella enterica with the antigenic formula 4,12:a:- ("Fulica-like") has been described as associated with harbour porpoises (Phocoena phocoena), most frequently recovered from lung samples. In the present study, lung tissue samples from 47 porpoises found along the Swedish coast or as bycatch in fishing nets were analysed, two of which were positive for S. enterica. Pneumonia due to the infection was considered the likely cause of death for one of the two animals. The recovered isolates were whole genome sequenced and found to belong to sequence type (ST) 416 and to be closely related to ST416/ST417 porpoise isolates from UK waters as determined by core-genome MLST. Serovars Bispebjerg, Fulica and Abortusequi were identified as distantly related to the porpoise isolates, but no close relatives from other host species were found. All ST416/417 isolates had extensive loss of function mutations in key Salmonella pathogenicity islands, but carried accessory genetic elements associated with extraintestinal infection such as iron uptake systems. Gene ontology and pathway analysis revealed reduced secondary metabolic capabilities and loss of function in terms of signalling and response to environmental cues, consistent with adaptation for the extraintestinal niche. A classification system based on machine learning identified ST416/417 as more invasive than classical gastrointestinal serovars. Genome analysis results are thus consistent with ST416/417 as a host-adapted and extraintestinal clonal population of S. enterica, which while found in porpoises without associated pathology can also cause severe opportunistic infections.
Assuntos
Genoma Bacteriano , Adaptação ao Hospedeiro , Phocoena , Salmonelose Animal/microbiologia , Salmonella enterica/genética , AnimaisRESUMO
There is increasing evidence that the â¼20 routinely monitored perfluoroalkyl and polyfluoroalkyl substances (PFASs) account for only a fraction of extractable organofluorine (EOF) occurring in the environment. To assess whether PFAS exposure is being underestimated in marine mammals from the Northern Hemisphere, we performed a fluorine mass balance on liver tissues from 11 different species using a combination of targeted PFAS analysis, EOF and total fluorine determination, and suspect screening. Samples were obtained from the east coast United States (US), west and east coast of Greenland, Iceland, and Sweden from 2000 to 2017. Of the 36 target PFASs, perfluorooctane sulfonate (PFOS) dominated in all but one Icelandic and three US samples, where the 7:3 fluorotelomer carboxylic acid (7:3 FTCA) was prevalent. This is the first report of 7:3 FTCA in polar bears (â¼1000 ng/g, ww) and cetaceans (<6-190 ng/g, ww). In 18 out of 25 samples, EOF was not significantly greater than fluorine concentrations derived from sum target PFASs. For the remaining 7 samples (mostly from the US east coast), 30-75% of the EOF was unidentified. Suspect screening revealed an additional 37 PFASs (not included in the targeted analysis) bringing the total to 63 detected PFASs from 12 different classes. Overall, these results highlight the importance of a multiplatform approach for accurately characterizing PFAS exposure in marine mammals.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Flúor , Groenlândia , Islândia , SuéciaRESUMO
Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn's disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.
Assuntos
Colangite Esclerosante , Microbioma Gastrointestinal , Transplante de Fígado , Colangite Esclerosante/complicações , Humanos , Projetos Piloto , Fatores de RiscoRESUMO
Short-, medium-, and long-chain chlorinated paraffins (SCCPs, MCCPs, and LCCPs) have a wide range of physical-chemical properties, indicating their varying bioaccumulation tendencies in marine and terrestrial ecosystems. However, there are few empirical data to reveal such bioaccumulation tendencies. In this study, we analyzed SCCPs, MCCPs, and LCCPs in samples from 18 species at both low and high trophic levels of marine and terrestrial ecosystems from the Scandinavian region collected during the past decade. These included fish, seabirds, marine mammals, and terrestrial birds and mammals. SCCPs, MCCPs, and LCCPs were present in all the species, with concentrations ranging from 26-1500, 30-1600, 6.0-1200 ng/g lipid, respectively. Although MCCPs and SCCPs predominated in most species, many terrestrial species had generally higher concentrations of LCCPs than marine species. Terrestrial raptors in particular accumulated higher concentrations of LCCPs, including C24/25-which are predominant among very-long-chain components. LCCP concentrations were highest and predominated (55% of total CPs) in peregrine falcons in this study, which is the first report where concentrations of LCCPs surpass those of SCCPs and MCCPs in wildlife. The results also indicate biomagnification of SCCPs, MCCPs, and LCCPs in both marine and terrestrial food chains, but in-depth studies of specific food webs are needed.
Assuntos
Hidrocarbonetos Clorados , Parafina , Animais , Ecossistema , Monitoramento Ambiental , Países Escandinavos e NórdicosRESUMO
Martin Folkes (1690-1754) was Newton's protégé, an English antiquary, mathematician, numismatist and astronomer who would in the latter part of his career become simultaneously president of the Royal Society and of the Society of Antiquaries. Folkes took a Grand Tour from March 1733 to September 1735, recording the Italian leg of his journey from Padua to Rome in his journal. This paper examines Folkes's travel diary to analyse his Freemasonry, his intellectual development as a Newtonian and his scientific peregrination. It shows how, in this latter area, how he used metrology to understand not only the aesthetics but also the engineering principles of antique buildings and artefacts, as well as their context and place in the Italian landscape. Using Folkes's diary, his account book of his journey in the Norwich archives, and his correspondence with other natural philosophers such as Francesco Algarotti (1712-1764), Anders Celsius (1701-1744) and Abbé Antonio Schinella Conti (1667-1749), this paper will also demonstrate to what extent Folkes's journey established his reputation as an international broker of Newtonianism, as well as the overall primacy of English scientific instrumentation to Italian virtuosi.
RESUMO
The level of PFAS (per- and polyfluorinated alkyl substances) contamination in freshwater and terrestrial Swedish environments in 2013/2014 was assessed by analyzing a range of perfluorinated alkyl acids, fluorotelomer acids, sulfonamides, sulfonamidoethanols and polyfluoralkyl phosphate diesters (diPAPs) in predator bird eggs. Stable isotopes ((13)C and (15)N) were analyzed to elucidate the dietary source. The tawny owl (Strix aluco, n=10) and common kestrel (Falco tinnunculus, n=40), two terrestrial species, and the osprey (Pandion haliaetus, n=30), a freshwater specie were included. In addition, a temporal trend (1997-2001, 2008-2009, 2013) in osprey was studied as well. The PFAS profile was dominated by perfluorooctane sulfonic acid (PFOS) in eggs from osprey and tawny owl, while for common kestrel perfluorinated carboxylic acids (∑PFCA) exceeded the level of PFOS. PFOS concentration in osprey eggs remained at the same level between 1997 and 2001 and 2013. For the long-chained PFCAs, there were a significant increase in concentrations in osprey eggs between 1997 and 2001 and 2008-2009. The levels of PFOS and PFCAs were about 10 and five times higher, respectively, in osprey compared to tawny owl and common kestrel. Evidence of direct exposure from PFCA precursor compounds to birds in both freshwater and terrestrial environment was observed. Low levels of diPAPs were detected in a few samples of osprey (<0.02-2.4ng/g) and common kestrel (<0.02-0.16ng/g) eggs, and 6:2 FTSA was detected in a majority of the osprey eggs (<6.3-52ng/g). One saturated telomer acid (7:3 FTCA), which is a transformation marker from precursor exposure, was detected in all species (<0.24-2.7ng/g). The (15)N data showed higher levels in osprey eggs compared to tawny owl and common kestrel, indicating that they feed on a 2-3 times higher trophic level. We conclude that ospreys are continuously exposed to PFAS at levels where adverse toxic effects have been observed in birds.
Assuntos
Exposição Ambiental , Monitoramento Ambiental/métodos , Falconiformes/metabolismo , Hidrocarbonetos Fluorados/metabolismo , Poluentes do Solo/metabolismo , Estrigiformes/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Ovos/análise , Poluentes Ambientais , SuéciaRESUMO
Our essay analyses a little-known book, Observations sur les eaux minerales des plusieurs provinces de France (1675), which is a study of French mineral waters, commissioned by and conducted at the French Royal Academy of Science (est. 1666). Its author, Samuel Cottereau Duclos (1598-1685), was a senior founding figure of the Academy, its chief chymist and one of its most influential members. We examine Observations with a focus on the changing attitudes towards chymical knowledge and practice in the French Academy and the Royal Society of London in the period 1666-84. Chymistry was a fundamental analytical tool for seventeenth-century natural historians, and, as the work of Lawrence Principe and William Newman has shown, it is central to understanding the 'long' Scientific Revolution. Much study has also been done on the developing norms of openness in the dissemination and presentation of scientific, and particularly chymical knowledge in the late seventeenth century, norms that were at odds with traditions of secrecy among individual chymists. Between these two standards a tension arose, evidenced by early modern 'vociferous criticisms' of chymical obscurity, with different strategies developed by individual philosophers for negotiating the emergent boundaries between secrecy and openness. Less well studied, however, are the strategies by which not just individuals but also scientific institutions negotiated these boundaries, particularly in the formative years of their public and political reputation in the late seventeenth century. Michael Hunter's recent and welcome study of the 'decline of magic' at the Royal Society has to some extent remedied these omissions. Hunter argues that the Society--as a corporate body--disregarded and avoided studies of magical and alchemical subjects in the late seventeenth century. Our examination problematizes these distinctions and presents a more complex picture.
Assuntos
Alquimia , Águas Minerais , França , História do Século XVI , História do Século XVII , FilosofiaRESUMO
In the seventeenth century, there were developing norms of openness in the presentation of scientific knowledge that were at odds with traditions of secrecy among chymists, particularly practitioners of chrysopoeia, or the transmutation of metals. This chapter analyzes how Dr. Robert Plot, the first professor of chymistry at Oxford, negotiated these boundaries within an institutional context. I first delineate his chymical and experimental practice, which incorporated procedures from medieval alchemical sources, particularly the Lullian corpus, as well as more novel practices from seventeenth-century chymistry. Then, I analyze how personal and institutional ambitions and economic considerations shaped to what extent Plot negotiated the boundaries between secrecy and the public dissemination of chymical knowledge.
Assuntos
Alquimia , Química/história , Inglaterra , História do Século XVIIRESUMO
The food enzyme α-amylase (4-α-d-glucan glucanohydrolase i.e. EC 3.2.1.1) is produced with the non-genetically modified Cellulosimicrobium funkei strain AE-AMT by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that the food enzyme did not give rise to safety concerns when used in seven food manufacturing processes. Subsequently, the applicant has requested to extend its use to include three additional processes. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of ten food manufacturing processes. As the food enzyme-total organic solids (TOS) are removed from the final foods in one food manufacturing process, the dietary exposure to the food enzyme-TOS was estimated only for the remaining nine processes. The dietary exposure was calculated to be up to 0.049 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (230 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 4694. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.
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The food enzyme pullulanase (pullulan 6-α-glucanohydrolase; EC 3.2.1.41) is produced with the non-genetically modified Pullulanibacillus naganoensis strain AE-PL by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in one food manufacturing process. Subsequently, the applicant has requested to extend its use to include seven additional processes and to revise the previous use level. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of eight food manufacturing processes. As the food enzyme-total organic solids (TOS) are not carried into the final foods in two food manufacturing processes, the dietary exposure was estimated only for the remaining six processes. The dietary exposure was calculated to be up to 0.004 mg TOS/kg body weight (bw) per day in European populations. The Panel evaluated the repeated dose 90-day oral toxicity study in rats submitted in the previous application and identified a no observed adverse effect level of 643 mg TOS/kg bw per day, the highest dose tested. When compared with the calculated dietary exposure, this resulted in a margin of exposure of at least 160,750. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use.
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The food enzyme triacylglycerol lipase (triacylglycerol acylhydrolase; EC 3.1.1.3) is produced with the non-genetically modified Aspergillus luchuensis strain AE-L by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in one food manufacturing process. Subsequently, the applicant has requested to extend its use to include four additional processes and to revise the previous use level. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of five food manufacturing processes. The dietary exposure to the food enzyme-total organic solids (TOS) was calculated to be up to 0.458 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (1726 mg TOS/kg bw per day, the highest dose tested), the Panel derived a revised margin of exposure of at least 3769. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use.