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1.
Sci Total Environ ; 952: 175793, 2024 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-39191329

RESUMEN

Anthropogenic pressures such as climate change and nutrient pollution are causing rapid changes in the marine environment. The relative influence of drivers of change on the plankton community remains uncertain, and this uncertainty is limiting our understanding of sustainable levels of human pressures. Plankton are the primary energy resource in marine food webs and respond rapidly to environmental changes, representing useful indicators of shifts in ecosystem structure and function. Categorising plankton into broad groups with similar characteristics, known as "lifeforms", can be useful for understanding ecological patterns related to environmental change and for assessing the state of pelagic habitats in accordance with the EU Marine Strategy Framework Directive and the OSPAR Commission, which mandates protection of the North-East Atlantic. We analysed 29 years of Continuous Plankton Recorder data (1993-2021) from the North-East Atlantic to examine how trends in plankton lifeform abundance changed in relation to one another and across gradients of environmental change associated with human pressures. Random forest models predicted between 57 % and 80 % of the variability in lifeform abundance, based on data not used to train the models. Observed variability was mainly explained by trends in other lifeforms, with mainly positively correlated trends, indicating bottom-up control and/or shared responses to environmental variability were prevalent. Longitude, bathymetry, mixed layer depth, the nitrogen-to­phosphorus ratio, and temperature were also significant predictors. However, contrasting influences of environmental drivers were detected. For example, small copepod abundance increased in warmer conditions whereas meroplankton, large copepods and fish larvae either decreased or were unchanged. Our findings highlight recent changes in stratification, reflected by variation in mixed layer depth, and imbalanced nutrient ratios are affecting multiple lifeforms, impacting the North-East Atlantic plankton community. To achieve environmental improvements in North-East Atlantic pelagic habitats, it is crucial that we continue to address climate change and reduce nutrient pollution.


Asunto(s)
Cambio Climático , Monitoreo del Ambiente , Plancton , Océano Atlántico , Ecosistema , Cadena Alimentaria
3.
Sci Total Environ ; 929: 172536, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38643886

RESUMEN

Oil and gas exploitation introduces toxic contaminants such as hydrocarbons and heavy metals to the surrounding sediment, resulting in deleterious impacts on marine benthic communities. This study combines benthic monitoring data over a 30-year period in the North Sea with dietary information on >1400 taxa to quantify the effects of active oil and gas platforms on benthic food webs using a multiple before-after control-impact experiment. Contamination from oil and gas platforms caused declines in benthic food web complexity, community abundance, and biodiversity. Fewer trophic interactions and increased connectance indicated that the community became dominated by generalists adapting to alternative resources, leading to simpler but more connected food webs in contaminated environments. Decreased mean body mass, shorter food chains, and the dominance of small detritivores such as Capitella capitata near to structures suggested a disproportionate loss of larger organisms from higher trophic levels. These patterns were associated with concentrations of hydrocarbons and heavy metals that exceed OSPAR's guideline thresholds of sediment toxicity. This study provides new evidence to better quantify and manage the environmental consequences of oil and gas exploitation at sea.


Asunto(s)
Biodiversidad , Monitoreo del Ambiente , Cadena Alimentaria , Invertebrados , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/análisis , Organismos Acuáticos , Mar del Norte , Metales Pesados/análisis , Yacimiento de Petróleo y Gas , Sedimentos Geológicos/química
4.
J Med Chem ; 67(8): 6610-6623, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38598312

RESUMEN

Inhibition of the biosynthesis of bacterial heptoses opens novel perspectives for antimicrobial therapies. The enzyme GmhA responsible for the first committed biosynthetic step catalyzes the conversion of sedoheptulose 7-phosphate into d-glycero-d-manno-heptose 7-phosphate and harbors a Zn2+ ion in the active site. A series of phosphoryl- and phosphonyl-substituted derivatives featuring a hydroxamate moiety were designed and prepared from suitably protected ribose or hexose derivatives. High-resolution crystal structures of GmhA complexed to two N-formyl hydroxamate inhibitors confirmed the binding interactions to a central Zn2+ ion coordination site. Some of these compounds were found to be nanomolar inhibitors of GmhA. While devoid of HepG2 cytotoxicity and antibacterial activity of their own, they demonstrated in vitro lipopolysaccharide heptosylation inhibition in Enterobacteriaceae as well as the potentiation of erythromycin and rifampicin in a wild-type Escherichia coli strain. These inhibitors pave the way for a novel treatment of Gram-negative infections.


Asunto(s)
Antibacterianos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Humanos , Bacterias Gramnegativas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Cristalografía por Rayos X , Sinergismo Farmacológico , Células Hep G2 , Modelos Moleculares , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/síntesis química , Zinc/química
5.
Front Microbiol ; 15: 1348171, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38389541

RESUMEN

Introduction: Intensive beef cattle production systems are frequently implicated as a source of bacteria that can be transferred to nearby humans and animals via effluent water, manure used as fertilizer, or airborne particulate matter. It is crucial to understand microbial population dynamics due to manure pack desiccation, antibiotic usage, and antibiotic alternatives within beef cattle and their associated feedyard environment. Understanding how bacterial communities change in the presence of antibiotics can also improve management practices for reducing the spread of foodborne bacteria. Methods: In this study, we aimed to compare the microbiomes within cattle feces, the feedyard environment and artificially produced airborne particulate matter as a function of pen change and treatment with tylosin or probiotics. We utilized 16S rRNA sequencing to compare bacterial communities among sample types, study days, and treatment groups. Results: Bacterial community diversity varied as a function of sampling day and pen change (old or new) within fecal and manure pack samples. Manure pack samples from old pens and new pens contained diverse communities of bacteria on days 0 and 84; however, by day 119 of the study these taxonomic differences were less evident. Particulate matter samples exhibited significant differences in community diversity and predominant bacterial taxa compared to the manure pack they originated from. Treatment with tylosin did not meaningfully impact bacterial communities among fecal, environmental, or particulate matter samples; however, minor differences in bacterial community structure were observed in feces from cattle treated with probiotics. Discussion: This study was the first to characterize and compare microbial communities within feces, manure pack, and airborne particulate matter from the same location and as a function of tylosin and probiotic treatment, and pen change. Although fecal and environmental samples are commonly used in research studies and other monitoring programs to infer public health risk of bacteria and antimicrobial resistance determinants from feedyard environments, our study suggests that these samples may not be appropriate to infer public health risk associated with airborne particulate matter.

6.
Glob Chang Biol ; 29(23): 6606-6619, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37814904

RESUMEN

Many studies predict shifts in species distributions and community size composition in response to climate change, yet few have demonstrated how these changes will be distributed across marine food webs. We use Bayesian Additive Regression Trees to model how climate change will affect the habitat suitability of marine fish species across a range of body sizes and belonging to different feeding guilds, each with different habitat and feeding requirements in the northeast Atlantic shelf seas. Contrasting effects of climate change are predicted for feeding guilds, with spatially extensive decreases in the species richness of consumers lower in the food web (planktivores) but increases for those higher up (piscivores). Changing spatial patterns in predator-prey mass ratios and fish species size composition are also predicted for feeding guilds and across the fish assemblage. In combination, these changes could influence nutrient uptake and transformation, transfer efficiency and food web stability, and thus profoundly alter ecosystem structure and functioning.


Asunto(s)
Ecosistema , Cadena Alimentaria , Animales , Cambio Climático , Teorema de Bayes , Océanos y Mares , Peces/fisiología
7.
Ir J Psychol Med ; 40(4): 592-600, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37592861

RESUMEN

OBJECTIVES: Mental health difficulties are often exacerbated during the perinatal period. Policy and guidelines are increasingly being used to enhance the quality of healthcare. We conducted a literature review of published research relating to pregnancy and breastfeeding in mental health policy. METHODS: Relevant terms were searched in Medline, CINAHL, APA PsycINFO and EMBASE for articles published in English from 1970 until 2020. Only papers that referenced policy, guidance, legislation or standards were included. While a systematic approach was used, the nature of the results necessitated a narrative review. RESULTS: Initially, 262 papers were identified, 44 met the inclusion criteria. Reproductive health is given sparse consideration in research relating to mental health policy. Despite this, some key areas emerged. These included: the need for proactive preconception psychoeducation, proactive screening of mothers of infants and young children for perinatal mental health issues, enhanced prescribing practice for women of child-bearing age, enhanced monitoring during pregnancy, development of safe modification of coercive practices should they need to be employed in emergency circumstances and targeted measures to reduce substance misuse. Themes that arose relating to breastfeeding and bonding are also described. CONCLUSIONS: Female reproductive health is often ignored in research relating to mental health policy, guidelines and standards. These tools need to be harnessed to promote good healthcare. Reproductive health should be included in the care plan of all mental health patients. These topics need to be integrated into existing relevant policies and not isolated to a separate policy.


Asunto(s)
Lactancia Materna , Atención a la Salud , Embarazo , Lactante , Humanos , Femenino , Preescolar , Salud Mental , Política de Salud
8.
Top Cogn Sci ; 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37439275

RESUMEN

In the modern world, many important tasks have become too complex for a single unaided individual to manage. Teams conduct some safety-critical tasks to improve task performance and minimize the risk of error. These teams have traditionally consisted of human operators, yet, nowadays, artificial intelligence and machine systems are incorporated into team environments to improve performance and capacity. We used a computerized task modeled after a classic arcade game to investigate the performance of human-machine and human-human teams. We manipulated the group conditions between team members; sometimes, they were instructed to collaborate, compete, or work separately. We evaluated players' performance in the main task (gameplay) and, in post hoc analyses, participant behavioral patterns to inform group strategies. We compared game performance between team types (human-human vs. human-machine) and group conditions (competitive, collaborative, independent). Adapting workload capacity analysis to human-machine teams, we found performance under both team types and all group conditions suffered a performance efficiency cost. However, we observed a reduced cost in collaborative over competitive teams within human-human pairings, but this effect was diminished when playing with a machine partner. The implications of workload capacity analysis as a powerful tool for human-machine team performance measurement are discussed.

9.
Sci Rep ; 13(1): 3110, 2023 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-36813881

RESUMEN

It is important to decipher the diversity and distribution of benthic dinoflagellates, as there are many morphologically indistinct taxa that differ from one another in production of potent toxins. To date, the genus Ostreopsis comprises twelve described species, of which seven are potentially toxic and produce compounds presenting a threat to human and environmental health. In this study, isolates previously identified as "Ostreopsis sp. 3" were sampled from the area where it was first reported, Rarotonga, Cook Islands, and have been taxonomically and phylogenetically characterised as Ostreopsis tairoto sp. nov. Phylogenetically, the species is closely related to "Ostreopsis sp. 8", O. mascarenensis, "O. sp. 4", O. fattorussoi, O. rhodesiae and O. cf. siamensis. Previously, it was considered a part of the O. cf. ovata complex but can be distinguished from O. cf. ovata based on the small pores identified on this study, and from O. fattorussoi and O. rhodesiae based on relative lengths of the 2' plates. No known palytoxin -like compounds were detected in strains investigated in this study. Strains of O. lenticularis, Coolia malayensis and C. tropicalis were also identified and described. This study advances our knowledge of biogeography, distribution, and toxins of Ostreopsis and Coolia species.


Asunto(s)
Dinoflagelados , Humanos , Océano Pacífico , Polinesia , Regiones Antárticas
10.
Biochemistry ; 61(20): 2229-2240, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36197914

RESUMEN

α-Carboxyketose synthases, including 3-deoxy-d-arabinoheptulosonate 7-phosphate synthase (DAHPS), are long-standing targets for inhibition. They are challenging targets to create tight-binding inhibitors against, and inhibitors often display half-of-sites binding and partial inhibition. Half-of-sites inhibition demonstrates the existence of inter-subunit communication in DAHPS. We used X-ray crystallography and spatially resolved hydrogen-deuterium exchange (HDX) to reveal the structural and dynamic bases for inter-subunit communication in Escherichia coli DAHPS(Phe), the isozyme that is feedback-inhibited by phenylalanine. Crystal structures of this homotetrameric (dimer-of-dimers) enzyme are invariant over 91% of its sequence. Three variable loops make up 8% of the sequence and are all involved in inter-subunit contacts across the tight-dimer interface. The structures have pseudo-twofold symmetry indicative of inter-subunit communication across the loose-dimer interface, with the diagonal subunits B and C always having the same conformation as each other, while subunits A and D are variable. Spatially resolved HDX reveals contrasting responses to ligand binding, which, in turn, affect binding of the second substrate, erythrose-4-phosphate (E4P). The N-terminal peptide, M1-E12, and the active site loop that binds E4P, F95-K105, are key parts of the communication network. Inter-subunit communication appears to have a catalytic role in all α-carboxyketose synthase families and a regulatory role in some members.


Asunto(s)
3-Desoxi-7-Fosfoheptulonato Sintasa , Isoenzimas , 3-Desoxi-7-Fosfoheptulonato Sintasa/química , Sitios de Unión , Catálisis , Comunicación , Cristalografía por Rayos X , Deuterio , Escherichia coli , Humanos , Isoenzimas/metabolismo , Ligandos , Fenilalanina/metabolismo , Fosfatos
11.
Curr Pharm Teach Learn ; 14(11): 1420-1430, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36137888

RESUMEN

BACKGROUND AND PURPOSE: Although pharmacists are first and foremost medication specialists and suppliers, in Australia they are also ideally positioned within the healthcare setting to encourage and support positive lifestyle choices in the community. Little has been done to assess their nutrition knowledge in over 20 years. We aimed to explore pharmacists' nutrition knowledge and associated practice and to subsequently develop and evaluate a short course to fill identified gaps. EDUCATIONAL ACTIVITY AND SETTING: The General Nutrition Knowledge Questionnaire was revised for testing nutrition knowledge in the pharmacy setting. Once validated, the questionnaire was distributed to pharmacists using social/professional media advertising. A short course was then developed, and its effectiveness assessed on final-year pharmacy students. FINDINGS: Pharmacists' (N = 258) mean score was 89.9 out of 121 (SD = 10.6) with significant variation. Nutrition education provision in practice was provided inconsistently and was associated with how strongly participants rated their own knowledge. Most pharmacists (95.7%) agreed they are well-placed to assist in disease burden reduction through nutrition education; however, most (98.4%) felt their knowledge needed improvement. The short course was well received by participants, deemed to be appropriate in context, and resulted in a median improvement in matched scores of 14.7% (P < .001) with no significant decline in knowledge when reassessed three weeks later (P = .383). SUMMARY: Pharmacists' nutrition knowledge and practice was variable. Further education can improve knowledge without significant time outlay and is likely to improve associated counselling practices.


Asunto(s)
Servicios Comunitarios de Farmacia , Farmacéuticos , Humanos , Rol Profesional , Actitud del Personal de Salud , Consejo
12.
Front Psychol ; 13: 834846, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35369146

RESUMEN

European identity is a complex, multi-faced and inherently imprecise concept relating to a range of socio-political and psychological factors. Addressing this topic in educational practice, particularly with respect to Higher Education students, constitutes a complex and open problem for research. This paper reports on an experimental study designed to explore the effectiveness of the educational game "RUEU?" in supporting university students in understanding the key socio-political issues regarding European identity. Quantitative data regarding Greek university students' (N = 92) attitudes to European identity, before and after playing the game, were collected. Students' performance of the game group (N = 46) was compared with that of a control group (N = 46) who explored the same issues about European identity through a tutor-guided discussion. The findings showed that both instructional interventions were effective but in different ways. The participants in the game-based group appeared more attached to the EU after the intervention and moved toward a more balanced description of their Greek and European identity. On the other hand, the students in the control group rated higher what "European identity" and being EU citizen means to them. The findings indicated the potential of game-based interventions to deliver not only academic content but also to promote students' reflection and influence them at an attitudinal and emotional level.

13.
Sci Rep ; 12(1): 3670, 2022 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-35256654

RESUMEN

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases with a common set of symptoms including cognitive and motor decline and vision loss. Naturally occurring sheep models of CLN5 and CLN6 disease display the key clinical features of NCL, including a progressive loss of vision. We assessed retinal histology, astrogliosis, and lysosomal storage accumulation in CLN5 affected (CLN5-/-) and CLN6 affected (CLN6-/-) sheep eyes and age-matched controls at 3, 6, 12, and 18 months of age to determine the onset and progression of retinal pathology in NCL sheep. The retina of CLN5-/- sheep shows progressive atrophy of the outer retinal layers, widespread gliosis, and accumulation of lysosomal storage in retinal ganglion cells late in disease. In contrast, CLN6-/- retina shows significant atrophy of all retinal layers, progressive gliosis, and earlier accumulation of lysosomal storage. This study has highlighted the differential vulnerability of retinal layers and the time course of retinal atrophy in two distinct models of NCL disease. This data will be valuable in determining potential targets for ocular therapies and the optimal timing of these therapies for protection from retinal dysfunction and degeneration in NCL.


Asunto(s)
Lipofuscinosis Ceroideas Neuronales , Degeneración Retiniana , Animales , Atrofia , Gliosis , Proteínas de la Membrana , Lipofuscinosis Ceroideas Neuronales/patología , Ovinos
14.
Chem Asian J ; 17(5): e202101328, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35034432

RESUMEN

Several new trivalent dinuclear rare earth 2,2'-methylenebis(6-tert-butyl-4-methylphenolate) (mbmp2- ) complexes with the general form [Ln2 (mbmp)3 (thf)n ] (Ln=Sm 1, Tb 2 (n=3), and Ho 3, Yb 4 (n=2), and a tetravalent cerium complex [Ce(mbmp)2 (thf)2 ] (5) have been synthesised by RTP (redox transmetallation/protolysis) reactions from lanthanoid metals, Hg(C6 F5 )2 and the biphenol mbmpH2 . These new complexes and some previously reported partially protonated rare earth biphenolate complexes [Ln(mbmp)(mbmpH)(thf)n ] react with lithium, aluminium, potassium and zinc organometallic reagents to form lanthanoid-main group heterobimetallic species. When reaction mixtures containing the Ln biphenolate complexes were treated with n-butyllithium, both molecular ([Li(thf)2 Ln(mbmp)2 (thf)n ] (Ln=La 6, Pr 7 (n=2) and Er 8, Yb 9, and Lu 10 (n=1)) and charge separated ([Li(thf)4 ][Ln(mbmp)2 (thf)2 ] (Ln=Y 11, Sm 12, Dy 13, and Ho 14) complexes were isolated. Treatment with trimethylaluminium also led to isolation of molecular ([AlMe2 Ln(mbmp)2 (thf)2 ] (Ln=Pr 15, Sm 16, and Tb 17)) and ionic [La(mbmp)(thf)5 ][AlMe2 (mbmp)] (18) complexes. One gadolinium-potassium ([K(thf)3 Gd(mbmp)2 (thf)2 ] (19)), and one ytterbium-zinc species ([ZnEtYb(mbmp)2 (thf)] (20)) were isolated from treatment of reaction mixtures with potassium bis(trimethylsilyl)amide and diethylzinc respectively.


Asunto(s)
Elementos de la Serie de los Lantanoides , Metales de Tierras Raras , Amidas , Cristalografía por Rayos X , Elementos de la Serie de los Lantanoides/química , Metales de Tierras Raras/química , Oxidación-Reducción
15.
J Cancer Educ ; 37(5): 1296-1303, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-33432468

RESUMEN

The patient-provider relationship is a key driver of patient satisfaction as it relates to overall healthcare experience. We surveyed patients undergoing radiation therapy to determine what they consider to be the most valued qualities in their interactions with the healthcare team. An ethics-approved 35-item patient satisfaction survey was developed in-house to gain insights on patients' perception of their relationship with the healthcare team throughout their cancer journey. There were 199 completed survey, median age 68 years, 54% women and 45% men. Almost all (95%) "agreed" or "strongly agreed" that their physicians had been sensitive and compassionate. Over 90% felt that they received adequate explanations about their treatment, and had their questions answered. The vast majority (93%) felt included in the decision-making process. Patients reported the 5 most highly rated qualities among their healthcare providers (HCPs) as knowledge, kindness, honesty, good communication, and a cheerful attitude. Overall satisfaction was high but areas for improvement were identified including being offered future appointments for further discussion, more information about clinical trials, other treatments, and community resources. Patients noted their HCPs tended to focus on the physical and emotional needs of patients, but spiritual and cultural needs were rarely addressed. Patients receiving radiotherapy reported high rates of satisfaction across many aspects of their care. These findings also reinforce the different aspects of holistic care that can be improved, and serve as a reminder to clinicians that patients perceive their role as more than just that of a medical expert.


Asunto(s)
Neoplasias , Satisfacción del Paciente , Anciano , Comunicación , Femenino , Personal de Salud/educación , Humanos , Masculino , Neoplasias/terapia , Relaciones Profesional-Paciente
17.
Environ Evid ; 11(1): 35, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39294784

RESUMEN

BACKGROUND: Many marine man-made structures (MMS), such as oil and gas platforms or offshore wind turbines, are nearing their 'end-of-life' and require decommissioning. Limited understanding of MMS decommissioning effects currently restricts the consideration of alternative management possibilities, often leaving complete removal as the only option in certain parts of the world. This evidence-base describes the ecosystem effects of marine MMS whilst in place and following cessation of operations, with a view to informing decision-making related to their potential decommissioning. METHOD: The protocol used to create this map was published a priori. Systematic searches of published, literature in English were conducted using three bibliographic databases, ten specialist organisational websites or repositories, and one search engine, up to early 2021. A total of 15,697 unique articles were identified as potentially relevant to our research questions, of which 2,230 were screened at the full-text level. Of that subset, 860 articles met all pre-defined eligibility criteria. A further 119 articles were identified through "snowballing" of references from literature reviews. The final database consists of 979 articles. For each article included, metadata were extracted for key variables of interest and coded into a database. REVIEW FINDINGS: The vast majority of eligible articles related to the presence of MMS (96.2%), while just 5.8% considered decommissioning. Overall, articles mainly considered artificial reefs (51.5% of all articles) but increasingly oil and gas (22%), shipwrecks (15.1%) and offshore wind (13.1%). Studies were distributed globally, but the majority focused on the United States, single countries within Europe, Australia, Brazil, China, and Israel; 25 studies spanned multiple countries. Consequently, the bulk of the studies focused on the North Atlantic (incl. Gulf of Mexico, North Sea, and Mediterranean Sea) and North Pacific Oceans. A further 12 studies had a global scope. Studies in majority reported on fish (53%) and invertebrates (41%), and were disproportionately focused on biological (81%) and ecological (48%) impacts. Physico-chemical (13%), habitat (7%), socio-cultural (7%), economic (4%) and functional (8%) outcomes have received less attention. The number of decommissioning studies has been increasing since ca. 2012 but remains noticeably low. Studies mostly focus on oil and gas infrastructures in the USA (Gulf of Mexico) and Northern Europe (North Sea), covering 9 different decommissioning options. CONCLUSIONS: This systematic map, the first of its kind, reveals a substantial body of peer-reviewed evidence relating to the presence of MMS in the sea and their impacts, but with considerable bias toward biological and ecological outcomes over abiotic and socio-economic outcomes. The map reveals extremely limited direct evidence of decommissioning effects, likely driven at least in part by international policy preventing consideration of a range of decommissioning options beyond complete removal. Despite evidence of MMS impacts continuing to grow exponentially since the early 1970s, this map reveals key gaps in evidence to support best practice in developing decommissioning options that consider environmental, social and economic effects. Relevant evidence is required to generate greater understanding in those areas and ensure decommissioning options deliver optimal ecosystem outcomes.

18.
ACS Infect Dis ; 7(12): 3292-3302, 2021 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-34761906

RESUMEN

3-Deoxy-d-arabinoheptulosonate-7-phosphate (DAHP) synthase catalyzes the first step in the shikimate biosynthetic pathway and is an antimicrobial target. We used an inhibitor-in-pieces approach, based on the previously reported inhibitor DAHP oxime, to screen inhibitor fragments in the presence and absence of glycerol 3-phosphate to occupy the distal end of the active site. This led to DAHP hydrazone, the most potent inhibitor to date, Ki = 10 ± 1 nM. Three trifluoropyruvate (TFP)-based inhibitor fragments were efficient inhibitors with ligand efficiencies of up to 0.7 kcal mol-1/atom compared with 0.2 kcal mol-1/atom for a typical good inhibitor. The crystal structures showed the TFP-based inhibitors binding upside down in the active site relative to DAHP oxime, providing new avenues for inhibitor development. The ethyl esters of TFP oxime and TFP semicarbazone prevented E. coli growth in culture with IC50 = 0.21 ± 0.01 and 0.77 ± 0.08 mg mL-1, respectively. Overexpressing DAHP synthase relieved growth inhibition, demonstrating that DAHP synthase was the target. Growth inhibition occurred in media containing aromatic amino acids, suggesting that growth inhibition was due to depletion of some other product(s) of the shikimate pathway, possibly folate.


Asunto(s)
3-Desoxi-7-Fosfoheptulonato Sintasa , Escherichia coli , 3-Desoxi-7-Fosfoheptulonato Sintasa/metabolismo , Dominio Catalítico , Escherichia coli/genética , Escherichia coli/metabolismo , Cinética , Fosfatos
19.
Dalton Trans ; 50(41): 14653-14661, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34585180

RESUMEN

A series of rare earth biphenolate complexes of the general form [Ln(mbmp)(mbmpH)(thf)3] (Ln = Y (1), Nd (2), Gd (3), Dy (4), Er (5), Tm (6) and Lu (7)) have been synthesised by redox transmetallation/protolysis (RTP) from the free rare earth metal, Hg(C6F5)2 and 2,2'-methylenebis(6-tert-butyl-4-methylphenol) (mbmpH2). The rare earth metal is six coordinate with one chelating biphenolate mbmp2- ligand and one unidentate monophenolate mbmpH- ligand. The yttrium complex, when crystallised from hot toluene or deuterated benzene, loses a coordinated thf and exhibits coordination through all three phenolate oxygen atoms, as well as the oxygen of the phenol, yielding two solvates [Y(mbmp)(mbmpH)(thf)2]·nsolv (solv = PhMe, n = 1 (8a) or C6D6, n = 2 (8b)). Of these rare earth complexes, the yttrium derivative (1) yielded the heterobimetallic complex [AlMe2Y(mbmp)2(thf)2] (9) when treated with trimethylaluminium, whereas all other complexes produced the transmetallation product [AlMe(mbmp)(thf)] (11). The dinuclear dysprosium complex [Dy2(mbmp)3(thf)3] (10) was isolated alongside 11 from the reaction of 4 with trimethylaluminium, suggesting trimethylaluminium instigates a redistribution reaction. The ROP activity of the mononuclear neodymium, dysprosium, lutetium, and aluminium complexes towards rac-lactide in toluene at 70 °C was found to be poor compared to rare earth complexes of monodentate aryloxides, but increased with increased rare earth ion size.

20.
Geochem Geophys Geosyst ; 22(5): e2020GC009588, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34220359

RESUMEN

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth-system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I-CDES) values for Intercarb-Carbon Dioxide Equilibrium Scale.

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