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1.
Fam Process ; 63(1): 130-150, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37431218

RESUMO

Two types of sexual beliefs, growth and destiny, have been found in past research to be differentially associated with sexual and relationship outcomes; however, past research has not explored these beliefs with dyadic data nor considered common intervening variables that might be pathways through which beliefs influence outcomes. Consequently, using the sexual wholeness model, we analyzed how couples' specific sexual beliefs (growth and destiny) influenced their sexual mindfulness, communication, and functioning within their couple relationships and how each of these variables influenced sexual satisfaction and harmonious sexual passion. Using a national sample of dyadic data from 964 sexually active individuals (482 heterosexual couples) who had been in a committed relationship for at least 2 years, we evaluated an actor/partner structural equation model with distinguishable dyads. We found that while sexual growth and destiny beliefs had a significant association with sexual mindfulness, communication, and functioning for both partners, sexual beliefs had no direct association with sexual satisfaction and harmonious sexual passion. Because growth beliefs had strong associations with sexual communication, it may be beneficial to help couples identify their implicit beliefs and encourage the development of sexual growth beliefs.


Assuntos
Atenção Plena , Parceiros Sexuais , Humanos , Comportamento Sexual , Satisfação Pessoal , Comunicação
2.
Mol Biol Evol ; 39(3)2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35192718

RESUMO

The indigenous population of the United Arab Emirates (UAE) has a unique demographic and cultural history. Its tradition of endogamy and consanguinity is expected to produce genetic homogeneity and partitioning of gene pools while population movements and intercontinental trade are likely to have contributed to genetic diversity. Emiratis and neighboring populations of the Middle East have been underrepresented in the population genetics literature with few studies covering the broader genetic history of the Arabian Peninsula. Here, we genotyped 1,198 individuals from the seven Emirates using 1.7 million markers and by employing haplotype-based algorithms and admixture analyses, we reveal the fine-scale genetic structure of the Emirati population. Shared ancestry and gene flow with neighboring populations display their unique geographic position while increased intra- versus inter-Emirati kinship and sharing of uniparental haplogroups, reflect the endogamous and consanguineous cultural traditions of the Emirates and their tribes.


Assuntos
Estruturas Genéticas , Genética Populacional , Consanguinidade , Geografia , Humanos , Emirados Árabes Unidos
3.
Nat Prod Rep ; 40(11): 1754-1808, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37555325

RESUMO

Covering literature to December 2022This review provides a comprehensive account of all natural products (500 compounds, including 17 semi-synthetic derivatives) described in the primary literature up to December 2022, reported to be capable of inhibiting the egg hatching, motility, larval development and/or the survival of helminths (i.e., nematodes, flukes and tapeworms). These parasitic worms infect and compromise the health and welfare, productivity and lives of commercial livestock (i.e., sheep, cattle, horses, pigs, poultry and fish), companion animals (i.e., dogs and cats) and other high value, endangered and/or exotic animals. Attention is given to chemical structures, as well as source organisms and anthelmintic properties, including the nature of bioassay target species, in vivo animal hosts, and measures of potency.


Assuntos
Anti-Helmínticos , Produtos Biológicos , Doenças do Gato , Doenças do Cão , Helmintos , Nematoides , Animais , Bovinos , Ovinos , Cavalos , Cães , Gatos , Suínos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/química , Anti-Helmínticos/uso terapêutico
4.
J Nat Prod ; 86(3): 633-637, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36655352

RESUMO

The myxomycete Fuligo septica, colloquially referred to as "dog vomit fungus", forms vibrant yellow fruiting bodies (aethalia) on wood chips during warm and humid conditions in spring. In 2018, ideal climatic conditions in Sydney, Australia, provided a rare opportunity to access abundant quantities of F. septica aethalia, which enabled the isolation, purification, structure elucidation, and biological screening of two avenalumamide pyrones, fuligopyrone (1) and fuligopyrone B (2). While 1 and 2 did not exhibit any appreciable biological activity, their significant UV absorption at 325 nm suggested they may be acting as transient sunscreens to help protect the fruiting mass from exposure to sunlight. In support of this hypothesis, exposing a solution of 2 to direct sunlight for 5 min resulted in rapid equilibration with a mixture of 2E,4Z-fuligopyrone B (10) and 2Z,4E-fuligopyrone B (11) photoisomers.


Assuntos
Ascomicetos , Mixomicetos , Animais , Cães , Mixomicetos/química , Raios Ultravioleta , Carpóforos , Austrália
5.
J Nat Prod ; 86(8): 2054-2058, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37526586

RESUMO

Turonicin A (1) was isolated from Streptomyces sp. MST-123921, which was recovered from soil collected on the banks of the Turon River in New South Wales, Australia. Turonicin A (1) is an amphoteric linear polyene polyketide featuring independent pentaene and tetraenone chromophores and is structurally related to linearmycins A-C (2-4). The structure of 1 was determined by detailed spectroscopic analysis and comparison to literature data. Bioinformatic analysis of the linearmycin biosynthetic gene cluster also allowed the previously unresolved absolute stereostructures of 2-4 to be elucidated. Turonicin A (1) exhibited very potent activity against the fungi Candida albicans (MIC 0.0031 µg/mL, 2.7 nM) and Saccharomyces cerevisiae (MIC 0.0008 µg/mL, 0.7 nM), moderate activity against the bacteria Bacillus subtilis (MIC 0.097 µg/mL, 85 nM) and Staphylococcus aureus (MIC 0.39 µg/mL, 340 nM), and no cytotoxicity against human fibroblasts, making it an attractive candidate for further development as a potential next-generation antibiotic scaffold.


Assuntos
Policetídeos , Streptomyces , Humanos , Antifúngicos/farmacologia , Policetídeos/farmacologia , Streptomyces/química , Austrália , Antibacterianos/química , Polienos/farmacologia , Testes de Sensibilidade Microbiana
6.
Antimicrob Agents Chemother ; 66(3): e0199121, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35007139

RESUMO

There is an urgent global need for new strategies and drugs to control and treat multidrug-resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes "traditional" and "nontraditional" antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 nontraditional), with 28 in phase 1, 32 in phase 2, 12 in phase 3, and 4 under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) were against mycobacteria, 15 (20%) were against C. difficile, and 4 (5%) were nontraditional agents with broad-spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores, and 4 of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical-priority pathogens. We believe that future antibacterial research and development (R&D) should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.


Assuntos
Infecções Bacterianas , Clostridioides difficile , Infecções por Bactérias Gram-Negativas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos
7.
Pharm Biol ; 60(1): 2049-2087, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36305538

RESUMO

CONTEXT: The emergence of zoonotic viruses in the last decades culminating with COVID-19 and challenges posed by the resistance of RNA viruses to antiviral drugs requires the development of new antiviral drugs. OBJECTIVE: This review identifies natural products isolated from Asian and Pacific medicinal plants with in vitro and in vivo antiviral activity towards RNA viruses and analyses their distribution, molecular weights, solubility and modes of action. MATERIALS AND METHODS: All data in this review was compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem and library search from 1961 to 2022. RESULTS: Out of about 350 molecules identified, 43 phenolics, 31 alkaloids, and 28 terpenes were very strongly active against at least one type of RNA virus. These natural products are mainly planar and amphiphilic, with a molecular mass between 200 and 400 g/mol and target viral genome replication. Hydroxytyrosol, silvestrol, lycorine, tylophorine and 12-O-tetradecanoylphorbol 13-acetate with IC50 below 0.01 µg/mL and selectivity index (S.I.) above 100 have the potential to be used for the development of anti-RNA virus leads. DISCUSSION AND CONCLUSIONS: The medicinal plants of Asia and the Pacific are a rich source of natural products with the potential to be developed as lead for the treatment of RNA viral infections.


Assuntos
Produtos Biológicos , COVID-19 , Plantas Medicinais , Vírus de RNA , Produtos Biológicos/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico
8.
Heredity (Edinb) ; 126(1): 63-76, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32699391

RESUMO

Understanding population genetic structure can help us to infer dispersal patterns, predict population resilience and design effective management strategies. For sessile species with limited dispersal, this is especially pertinent because genetic diversity and connectivity are key aspects of their resilience to environmental stressors. Here, we describe the population structure of Ircinia campana, a common Caribbean sponge subject to mass mortalities and disease. Microsatellites were used to genotype 440 individuals from 19 sites throughout the Greater Caribbean. We found strong genetic structure across the region, and significant isolation by distance across the Lesser Antilles, highlighting the influence of limited larval dispersal. We also observed spatial genetic structure patterns congruent with oceanography. This includes evidence of connectivity between sponges in the Florida Keys and the southeast coast of the United States (>700 km away) where the oceanographic environment is dominated by the strong Florida Current. Conversely, the population in southern Belize was strongly differentiated from all other sites, consistent with the presence of dispersal-limiting oceanographic features, including the Gulf of Honduras gyre. At smaller spatial scales (<100 km), sites showed heterogeneous patterns of low-level but significant genetic differentiation (chaotic genetic patchiness), indicative of temporal variability in recruitment or local selective pressures. Genetic diversity was similar across sites, but there was evidence of a genetic bottleneck at one site in Florida where past mass mortalities have occurred. These findings underscore the relationship between regional oceanography and weak larval dispersal in explaining population genetic patterns, and could inform conservation management of the species.


Assuntos
Estruturas Genéticas , Oceanografia , Região do Caribe , Humanos
9.
Arch Dis Child Educ Pract Ed ; 106(5): 264-268, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988964

RESUMO

The COVID-19 pandemic has changed how we work in paediatrics with increasing use of virtual consultations. When optimised, a great deal can be achieved through video consultation compared with telephone, but accessibility and clinical risk need to be carefully considered and managed. This article aims to provide a structured approach with top tips for planning and delivering video consultations effectively in paediatrics.


Assuntos
COVID-19 , Tecnologia da Informação , Encaminhamento e Consulta , Telemedicina , Adolescente , Criança , Humanos , Pandemias , SARS-CoV-2
10.
Conserv Biol ; 34(6): 1492-1502, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32390269

RESUMO

The key to the conservation of harvested species is the maintenance of reproductive success. Yet for many marine species large, old, individuals are targeted despite their disproportionate contribution to reproduction. We hypothesized that a combination of no-take marine protected areas (MPAs) and harvest slot limits (maximum and minimum size limits) would result in the conservation of large spawning individuals under heavy harvest. We tested this approach under different harvest intensities with a 2-sex, stage-structured metapopulation model for the Caribbean spiny lobster (Panulirus argus). P. argus is intensively harvested in the Caribbean, and in many localities large, mature individuals no longer exist. No-take MPAs and harvest slot limits combined, rebuilt and maintained large mature individuals even under high harvest pressure. The most conservative model (a 30% MPA and harvest slot limit of 75-105 mm) increased spawner abundance by 5.53E12 compared with the fishing status quo at the end of 30 years. Spawning stock abundance also increased by 2.76-9.56E12 individuals at a high harvest intensity over 30 years with MPAs alone. Our results demonstrate the potential of MPAs and harvest slot limits for the conservation of large breeding individuals in some marine and freshwater environments. Decisions on which management strategy best suits a fishery, however, requires balancing what is ecologically desirable with what is economically and socially feasible.


Conservación de Stocks Reproductivos por medio de Límites de Espacios de Producción y Áreas Protegidas de Cero Captura Resumen La clave para la conservación de las especies en criaderos es la manutención del éxito reproductivo. Aún así, para muchas especies marinas los individuos grandes y viejos son seleccionados a pesar de su contribución desproporcionada para la reproducción. Nuestra hipótesis supone que una combinación de áreas marinas protegidas (AMPs) de cero captura y los límites de espacio de producción (límites máximos y mínimos de tamaño) resultaría en la conservación de individuos reproductivos grandes durante una producción intensiva. Probamos esta estrategia bajo diferentes intensidades de crianza con un modelo metapoblacional de dos sexos y estructurado por etapas aplicado a la langosta espinosa del Caribe (Panulirus argus). P. argus es producida intensivamente en el Caribe y en muchas de las localidades, los individuos grandes y maduros ya no existen. La combinación de las AMPs de cero captura y los límites de espacio de producción regeneró y mantuvo individuos grandes y maduros incluso bajo una presión alta de producción. El modelo más conservador (un 30% de MPA y un límite de espacio de producción de 75-105 mm) incrementó la abundancia de individuos reproductivos por 5.53E12 comparado con el status quo de la pesca después de treinta años. La abundancia del stock reproductivo también incrementó por 2.76-9.56E12 individuos en una intensidad alta de producción durante 30 años sólo con las AMPs. Nuestros resultados demuestran el potencial de las AMPs y los límites de espacio de producción para la conservación de individuos reproductivos grandes en algunos ambientes marinos y de agua dulce. Sin embargo, las decisiones sobre cuál es la mejor estrategia de manejo para una pesquería requieren del equilibrio entre lo que es ecológicamente deseable y lo que es económica y socialmente factible.


Assuntos
Conservação dos Recursos Naturais , Palinuridae , Animais , Pesqueiros , Peixes , Reprodução
11.
Fam Process ; 59(3): 1334-1352, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31334853

RESUMO

In the context of relationship trauma, partners' reactive patterns of engagement can disrupt and derail attempts at relationship correction and healing. A circumplex typology of couple patterns of engagement in relational trauma context is defined in terms of partners' underlying views of self in relation to other (VSIRO). VSIRO is conceptualized along a continuum anchored at opposite poles by inflated (self-aggrandizing) versus collapsed (self-abnegating) VSIRO, with a balanced (egalitarian) VSIRO, characterized by accountability and forbearance, as the target position. The circumplex model delineates four problematic couple configurations-a dejected couple, a taker-enabler couple, an ultimate fighting couple, and a debtor-collector couple. Where problematic engagement occurs, therapists need to reshape couple engagement toward the balanced, egalitarian position prior to relational trauma work. Clinical vignettes depict these couples and springboard an analysis of unique needs and interventions associated with each couple configuration. Reshaping couple patterns of engagement using a circumplex model of couple configurations is an essential prerequisite to effective and ethical relational trauma work.


Assuntos
Terapia de Casal , Relações Interpessoais , Modelos Psicológicos , Parceiros Sexuais/psicologia , Feminino , Humanos , Masculino
12.
Environ Geochem Health ; 42(10): 3263-3279, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32335849

RESUMO

Fragmented ultramafic bodies in New England were important mineral resources until the early twentieth century, yet few studies have addressed their potential to release trace metals to terrestrial and aquatic environments. Here, we evaluate the release of four trace metals (Cr, Co, Mn, and Ni) from a historic serpentine-talc "soapstone" quarry in Blandford, MA, USA. Soil pits, sediment and rock samples, and stream water samples were collected from upslope undisturbed areas, within the mine spoils and mine face, and downslope of the mine. In order to provide a bottom-up approach for understanding metal release, careful petrographic analysis, electron-dispersive spectroscopy, and wavelength-dispersive spectroscopy were employed to provide first-order insight into the mineralogy of the deposit and a determination of potential metal-bearing phases. Trace metals were primarily observed in ultramafic sheet silicates, primary Fe-oxides, and interstitial weathering-related sulfates. Bulk rock concentrations were Cr (1550 mg kg-1), Co (230 mg kg-1), Mn (1100 mg kg-1), and Ni (1960 mg kg1); Cr, Co, and Ni were elevated relative to the surrounding country rock. However, soils and sediments total concentrations were comparable to background soil concentrations: Cr (119 mg kg-1), Co (73 mg kg-1), Mn (894 mg kg-1), and Ni (65 mg kg-1). Moreover, < 0.5% of the total concentrations were bioavailable (0.1 M ammonium acetate extraction), implying that metals are present as insoluble forms. However, ~ 20% of the total Cr, Mn, Ni, and Co concentrations were strong acid extractable, suggesting mobilization over the coming decades. Stream water concentrations of Mn and Cr were < 50 µg L-1, below concentrations outlined by USEPA drinking water standards, and WHO water guidelines for Ni. These results suggest that transport of Cr, Mn, Ni, and Co from the serpentine-talc as dissolved compounds or sediments is limited by retention within silicate and oxides.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Mineração , Poluentes do Solo/análise , Solo/química , Disponibilidade Biológica , Massachusetts
13.
Nat Prod Rep ; 36(1): 35-107, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30003207

RESUMO

Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.


Assuntos
Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , Conformação Molecular , Reprodutibilidade dos Testes
15.
J Antimicrob Chemother ; 74(3): 582-593, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30445429

RESUMO

BACKGROUND: Polymyxin B and E (colistin) have been pivotal in the treatment of XDR Gram-negative bacterial infections; however, resistance has emerged. A structurally related lipopeptide, octapeptin C4, has shown significant potency against XDR bacteria, including polymyxin-resistant strains, but its mode of action remains undefined. OBJECTIVES: We sought to compare and contrast the acquisition of resistance in an XDR Klebsiella pneumoniae (ST258) clinical isolate in vitro with all three lipopeptides to potentially unveil variations in their mode of action. METHODS: The isolate was exposed to increasing concentrations of polymyxins and octapeptin C4 over 20 days. Day 20 strains underwent WGS, complementation assays, antimicrobial susceptibility testing and lipid A analysis. RESULTS: Twenty days of exposure to the polymyxins resulted in a 1000-fold increase in the MIC, whereas for octapeptin C4 a 4-fold increase was observed. There was no cross-resistance observed between the polymyxin- and octapeptin-resistant strains. Sequencing of polymyxin-resistant isolates revealed mutations in previously known resistance-associated genes, including crrB, mgrB, pmrB, phoPQ and yciM, along with novel mutations in qseC. Octapeptin C4-resistant isolates had mutations in mlaDF and pqiB, genes related to phospholipid transport. These genetic variations were reflected in distinct phenotypic changes to lipid A. Polymyxin-resistant isolates increased 4-amino-4-deoxyarabinose fortification of lipid A phosphate groups, whereas the lipid A of octapeptin C4-resistant strains harboured a higher abundance of hydroxymyristate and palmitoylate. CONCLUSIONS: Octapeptin C4 has a distinct mode of action compared with the polymyxins, highlighting its potential as a future therapeutic agent to combat the increasing threat of XDR bacteria.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla , Klebsiella pneumoniae/efeitos dos fármacos , Lipopeptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Polimixina B/farmacologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Mutação , Sequenciamento Completo do Genoma
16.
J Anim Ecol ; 88(11): 1684-1695, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31325164

RESUMO

Marine sponges are hosts to large, diverse communities of microorganisms. These microbiomes are distinct among sponge species and from seawater bacterial communities, indicating a key role of host identity in shaping its resident microbial community. However, the factors governing intraspecific microbiome variability are underexplored and may shed light on the evolutionary and ecological relationships between host and microbiome. Here, we examined the influence of genetic variation and geographic location on the composition of the Ircinia campana microbiome. We developed new microsatellite markers to genotype I. campana from two locations in the Florida Keys, USA, and characterized their microbiomes using V4 16S rRNA amplicon sequencing. We show that microbial community composition and diversity is influenced by host genotype, with more genetically similar sponges hosting more similar microbial communities. We also found that although I. campana was not genetically differentiated between sites, microbiome composition differed by location. Our results demonstrate that both host genetics and geography influence the composition of the sponge microbiome. Host genotypic influence on microbiome composition may be due to stable vertical transmission of the microbial community from parent to offspring, making microbiomes more similar by descent. Alternatively, sponge genotypic variation may reflect variation in functional traits that influence the acquisition of environmental microbes. This study reveals drivers of microbiome variation within and among locations, and shows the importance of intraspecific variability in mediating eco-evolutionary dynamics of host-associated microbiomes.


Assuntos
Microbiota , Poríferos , Animais , Florida , Geografia , Filogenia , RNA Ribossômico 16S
17.
J Nat Prod ; 82(11): 3165-3175, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31625738

RESUMO

The termite nest-derived fungus Trichoderma virens CMB-TN16 cultivated on rice-based media produced seven new first-in-class trimeric sesquiterpenes, trivirensols A-G (11-17). Structures inclusive of absolute configurations were assigned by detailed spectroscopic analysis and biosynthetic considerations. Although trivirensols exhibit no cytotoxicity to mammalian carcinoma cells, selected examples are bacteriostatic against vancomycin-resistant Enterococcus faecalis (VRE). Structure-activity relationship (SAR) investigations combined with in situ chemical stability studies documented bacteriostatic activity for trivirensols A (11) and B (12) and the co-metabolite divirensols A (4), B (5), and G (10), all of which share a common terminal butenolide. Significantly, SAR studies also revealed bacteriostatic activity for trivirensols C (13) and G (17) and the co-metabolite divirensol C (6), all of which share a common hydrated butenolide terminal. Of note, when exposed to VRE cell cultures, the hydrated butenolides 6, 13, and 17 undergo rapid in situ dehydration to corresponding butenolides, suggesting hydrated butenolides are a pro-drug form of the butenolide VRE bacteriostatic pharmacophore.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Isópteros/microbiologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Trichoderma/química , Animais , Austrália , Biotransformação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Trichoderma/isolamento & purificação
18.
Arch Sex Behav ; 48(8): 2233-2249, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30014336

RESUMO

Although research has suggested a net negative influence of sexual media on sexual quality, enough researchers have found results suggesting that sexual media has no effect or a positive influence that the matter warrants further investigation. We present an organizational framework utilizing primarily the acquisition, activation, application model (3AM), and the Antecedents-Context-Effects model (ACE) to reconcile these apparently contradictory claims. By synthesizing these theories, we suggest that to truly understand the impact of sexual media on sexual quality, four factors must be taken into account: (1) the content of the sexual media being viewed, (2) the difference between short-term and long-term sexual quality, (3) the influence of exclusivity, formativeness, resonance, and reinforcement in moderating the extent to which the portrayed sexual script is applied (influences attitudes and behavior), and (4) the couple context for congruency of use, script application, and moral paradigms. While acknowledging the many nuances that should be considered, we ultimately argue that when considering these factors simultaneously, the overall scripts presented in sexual media are congruent with pursuing factors for short-term sexual quality and incongruent with pursuing factors for long-term sexual quality.


Assuntos
Literatura Erótica/psicologia , Comportamento Sexual/psicologia , Mídias Sociais/normas , Feminino , Humanos , Masculino
19.
Adv Exp Med Biol ; 1185: 119-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884599

RESUMO

Hammerhead ribozymes (hhRzs), RNA enzymes capable of site-specific cleavage of arbitrary target mRNAs, have faced significant hurdles in development and optimization as gene therapeutics for clinical translation. Chemical and biological barriers must be overcome to realize an effective therapeutic. A new Facilitated ribozyme has been identified with greatly enhanced kinetic properties that lead new insight on the capacity of ribozymes to target mutant genes to treat inherited retinal degenerations.


Assuntos
RNA Catalítico/uso terapêutico , Degeneração Retiniana/terapia , Humanos , RNA Mensageiro
20.
Mycopathologia ; 184(2): 273-281, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707338

RESUMO

The fertilizing properties of bird manure, or guano, have played an important role in plant cultivation for thousands of years. Research into its chemical composition by Unger in 1846 identified a novel compound, now known as guanine, a purine base that is essential for DNA and RNA biosynthesis and cell signalling. Nitrogen-rich guano can also harbour human pathogens, one significant example being the fungal pathogen Cryptococcus neoformans. Historically associated with pigeon droppings, C. neoformans is able to infect immunocompromised individuals with the aid of a number of adaptive virulence traits. To gain insight into this niche, a quantitative analysis of pigeon guano was performed by LC/MS to determine the concentrations of purines present. Guanine was found in abundance, in particular, in aged guano samples that contained 156-296 µg/g [w/w] compared to 75 µg/g in fresh guano. Adenine concentrations were more consistent between fresh and aged samples, 13 µg/g compared to 10-15 µg/g, respectively. C. neoformans strains that lack key enzymes of the de novo purine synthesis pathway and are guanine or adenine auxotrophs displayed differences in their ability to exploit this substrate: growth of a guanine auxotrophic mutant (gua1Δ) was partially restored on 30% pigeon guano media, but an adenine auxotrophic mutant (ade13Δ) was unable to grow. We conclude that while purine salvage is likely a useful resource-saving mechanism, alone it is not sufficient to fully provide the purines required by wild-type C. neoformans growing in its guano niche.


Assuntos
Columbidae , Cryptococcus neoformans/crescimento & desenvolvimento , Fezes/química , Purinas/análise , Animais , Cromatografia Líquida , Cryptococcus neoformans/metabolismo , Espectrometria de Massas , Viabilidade Microbiana , Purinas/metabolismo
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